Molecular-Mechanical studies of the mismatched base analogs of d(CGCGAATTCGCG)2:d(CGTGAATTCGCG)2, d(CGAGAATTCGCG)2, d(CGCGAATTCACG)2, d(CGCGAATTCTCG)2, and d(CGCAGAATTCGCG)·d(CGCGAATTCGCG)

Molecular-mechanical simulations have been carried out on “mismatched base” analogs of the DNA double-helical structure d(CGCGAATTCGCG)₂, in which the base pairs CG at the 3 and 10 positions have been replaced by CA, AG, TC, and TG base pairs, as well as an insertion analog in which an extra adenine has been incorporated into one strand of the above structure between bases 3 and 4. The results of these simulations (calculated relative stabilities, structures, and nmr ring-current shifts) have been compared with calorimetric and nmr data. The calculated relative stabilities of the double-helical parent dodecamer and the various “wobble” base pairs qualitatively correlate with the experimental melting temperatures. The base-pairing structure for the GT wobble pair is in agreement with that previously determined from nmr experiments. For the GA base pair, the structure with both bases anti has a slightly more favorable energy from base pairing and stacking than a structure with non-Watson-Crick H-bonding with adenine syn, in agreement with nmr experiments. The CA wobble base is calculated to favor an adenine 6NH₂ …? cytosine N3 H-bond over cytosine 4NH₂ …? adenine N1, again, in agreement with nmr experiments. There is no definitive experimental data on the TC base pair, but the existence of (somewhat long and weak) H-bonds involving cytosine 4NH₂ …? thymine 4CO and cytosine N3 …? thymine HN3 seems reasonable. We find a structure in which the extra adenine base of the insertion analogs sits “inside” the double helix.     

Feather mites (Acarina) of the parakeet, Melopsittacus undulatus (Shaw) (Aves: Psittacidae)

The parakeet (or budgerigar) has been transported to many regions of the world. Two species of feather mites, Protolichus lunula (Robin) (Pterolichoidea: Pterolichidae) and Dubininia melopsittaci n. sp. (Analgoidea: Xolalgidae), are specific to this host; from distribution records, these ectoparasites probably have been distributed worldwide with their hosts.     

Synthesis, characterization, and antitumor activity of 1,2-bis(diphenylphosphino) ethane platinum(II) and palladium(II) complexes

A number of 1,2-bis(diphenylphosphino)ethane monomeric platinum(II) and palladium(II) complexes have been synthesized in light of their potential antitumor activity. The metal center is coordinated with a number of carboxylate anions in the cis-configuration. These complexes have been characterized by elemental analysis, conductivity measurement, and various spectroscopic techniques [IR and 195Pt NMR]. In vivo screening tests for activity of these complexes were performed against the L1210/0 murine leukemia cancer model, but none displayed a significant level of antitumor activity.     

Trans-bis(benzo(1,3)-thiazole)bis(N,N-dimethylformamide)bis(N-thiocyanato)-cobalt(II): spectroscopy,thermal analysis and crystal structure

Disolution of Co(bzt)₂(NCS)₂ (bzt = benzo 1,3- thiazole) in dimethyl formamide (dmf) produces Co(bzt)₂(NCS)₂(dmf)₂. The stoichionmetry of the complex has been established by a combination of chemical (C, H, N) and thermal analysis. The comlex has an octahedral structure with pairs of ligands in trans configuration as well as a CoN₄O₂ coordination sphere with CoN distances of 2.185(2) Å (bzt); 2.082(2) Å (NCS) and CoN(dmf) of 2.118(2) Å. The infrared and electronic absorption spectra are consistent with this arrangement.     

Synthesis, Copper(II) Complexation, (64)Cu-Labeling, and Bioconjugation of a New Bis(2-pyridylmethyl) Derivative of 1,4,7-Triazacyclononane

A new ligand derivative of 1,4,7-triazacyclononane (TACN), 2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetic acid ( 6), has been synthesized and its complexation behavior toward Cu2+ ions investigated. The ligand 6 has been characterized by spectroscopic methods, and a molecular structure of a corresponding Cu(II) complex has been elucidated by single-crystal X-ray analysis. The suitability of 6 for conjugation to peptide substrates has been shown by amide coupling of 6 to the stabilized derivative of bombesin (BN), beta Ala-beta Ala-[Cha13, Nle14]BN(7-14), to give the conjugate 8. The free ligand 6 and the bioconjugate 8 were labeled with 64Cu2+, and the resulting complexes, 64Cu subset6 and 64Cu subset8 , were found to be stable in the presence of a large excess of a competing ligand (cyclam) or copper-seeking superoxide dismutase (SOD), as well as in rat plasma. Biodistribution studies of 64Cu subset8 in Wistar rats showed a high activity uptake into the pancreas (5.76 +/- 0.25 SUV, 5 min p.i.; 3.93 +/- 0.25 SUV, 1 h p.i.), which is the organ with high levels of gastrin-releasing peptide receptor (GRPR). This receptor is overexpressed in a large number of breast and prostate carcinomas. The novel 64Cu subset6 complex had a dominating influence on the nonspecific activity biodistribution of its BN conjugate, since the distribution data of 64Cu subset6 are similar to those of 64Cu subset8 . The 64Cu complexes exhibited a low activity accumulation in the liver tissue and an extensive renal clearance, which was distinctively different to the biodistribution of 64CuCl 2, suggesting that 64Cu subset6 does not undergo significant demetalation, but rather exhibits high in vivo stability.     

Late Carnian (Tuvalian,Tropites dilleri zone) ostracods (Crustacea) from the Mufara Formation (Monte Scalpello,Central-Eastern Sicily,Italy)

Ostracod association from the Upper Triassic (Tropites dilleri zone of the Carnian stage) of the sedimentary succession (Mufara Formation) exposed along the east side of Monte Scalpello (Catenanuova, central eastern Sicily) has been studied for the first time. The specimens, silicified, are rare but well preserved and often consist of complete carapaces. They belong to eight families: Healdiidae, Cavellinidae, Bairdiidae, Acratiidae, Bythocyprididae, Pontocyprididae, Judahellidae, Glorianellidae. Twenty-three taxa have been listed; the family Bairdiidae is the most represented among all the others with fifteen species. Four species are new: Bairdia scaliae n. sp., Acratia maugerii n. sp., “Anchistrocheles” gemmellaroi n. sp. and Judahella? montanarii n. sp. Other species are left in open nomenclature because of the lack of specimens.     

Synthesis, catalytic activity, phosphatase inhibition activity, and X-ray structural characterization of vanadium scorpionate complexes, (Tpms)VCl2(DMF) and (Tpms)VOCl(DMF)

The complexes (Tpms)VCl₂(DMF) (1), and (Tpms)VOCl(DMF) (2), have been synthesized and characterized. Complex 2 has also been structurally characterized via X-ray diffractometry. The vanadium(IV) center possesses a square pyramidal/distorted octahedral geometry with a facially coordinating Tpms⁻ ligand in a κ³-N,N,O coordination mode. The complex is the first structurally characterized example of a vanadium(IV) complex with Tpms⁻. Complex 2 shows catalytic activity towards oxidation of 3,5-di-tert-butyl catechol and also exhibits phosphatase inhibition characteristics on alkaline phosphatase. Tpms⁻ = trispyrazolylmethanesulfonate; DMF = N,N-dimethylformamide.     

Polyelectrolyte complexes between (cross-linked) N-carboxyethylchitosan and (quaternized) poly[2-(dimethylamino)ethyl methacrylate]: preparation, characterization, and antibacterial properties

Novel polyelectrolyte complexes (PECs) between N-carboxyethylchitosan (CECh) and well-defined (quaternized) poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) have been obtained. The modification of chitosan into CECh allows the preparation of PECs in a pH range in which chitosan cannot form complexes. The CECh/PDMAEMA complex is formed in a narrow pH range around 7. The quaternization of the tertiary amino groups of PDMAEMA enables complex formation with CECh both in neutral and in alkaline medium. Cross-linked CECh is also capable of forming complexes with (quaternized) PDMAEMA. The antibacterial activity of (cross-linked) CECh, (quaternized) PDMAEMA, and their complexes against Escherichia coli has been evaluated. In contrast to (quaternized) PDMAEMA, (cross-linked) CECh exhibits no antibacterial activity. The complex formation between cross-linked CECh and (quaternized) PDMAEMA results in a loss of the inherent antibacterial activity of the latter in neutral medium. In acidic medium, the complexes exhibit strong antibacterial activity due to complex disintegration and release of (quaternized) PDMAEMA.     

Differences in Fe(III) reduction in the hyperthermophilic archaeon, Pyrobaculum islandicum, versus mesophilic Fe(III)-reducing bacteria

The discovery that all hyperthermophiles that have been evaluated have the capacity to reduce Fe(III) has raised the question of whether mechanisms for dissimilatory Fe(III) reduction have been conserved throughout microbial evolution. Many studies have suggested that c-type cytochromes are integral components in electron transport to Fe(III) in mesophilic dissimilatory Fe(III)-reducing microorganisms. However, Pyrobaculum islandicum, the hyperthermophile in which Fe(III) reduction has been most intensively studied, did not contain c-type cytochromes. NADPH was a better electron donor for the Fe(III) reductase activity in P. islandicum than NADH. This is the opposite of what has been observed with mesophiles. Thus, if previous models for dissimilatory Fe(III) reduction by mesophilic bacteria are correct, then it is unlikely that a single strategy for electron transport to Fe(III) is present in all dissimilatory Fe(III)-reducing microorganisms.     

Preparation, UV-Vis, IR and H NMR spectra, and molecular structure of the complex ion (η-carbonato)(α,α,α,α-tetrakis (o-pivalamidophenyl)porphinato)ferrate(III)

An iron(III) porphyrin complex containing a bidentate carbonato axial ligand has been synthesized for the first time and fully characterized by UV-Vis, IR and ¹H NMR spectroscopies and X-ray crystallography. Proton NMR data for the isolated species is in accordance with high-spin (S = 5/2) ferric derivative. The crystal structure of the (cryptand-222)potassium(+) (dihaptocarbonato)(α,α,α,α-terakis(o-pivalamidophenyl)(porphinato)ferrate(III) chlorobenzene has been determined. This structure confirms the high-spin-state of the carbonato derivative and shows that the coordination sphere of the iron atom is strongly affected by the asymmetric bidentate (η²) mode of the carbonato axial ligand.     

Ventilation of the branchial chambers in the amphibious West African freshwater crab,Sudanonautes (Convexonautes) aubryi monodi (Balss, 1929) (Brachyura,Potamonautidae)

The anatomy of the respiratory system of the savanna-zone African freshwater crab, Sudanonautes (Convexonautes) aubryi monodi [Balss, 1929], has been examined and has been found to be adapted for both aerial and aquatic gas exchange. The activities of the scaphognathites and the directions of flow of the ventilatory stream have been recorded in stressed, active and resting specimens during their exposure to a wide range of conditions from deep water to dry land.Ventilation of the branchial chambers during aquatic gas exchange in Sudanonautes kept in deep water is shown to consist of a rapid, predominantly forward water flow similar to that of fully-aquatic species. Ventilation of the branchial chambers during aerial gas exchange in Sudanonautes on land is shown to consist of a relatively slow forward air flow. This flow is continuous in post-operative crabs, pulsatile in active crabs and completely immobile in resting crabs.A second method of ventilation of the branchial chambers during aerial gas exchange is shown to consist of a pulsatile reversed air flow. This occurs (1) when Sudanonautes is kept in very shallow water and active or stressed; (2) when it has recently moved on to land; and (3) when it is completely immersed and exhibiting aerial gas exchange under water. The unusual phenomenon of aerial gas exchange under water is reported here for the first time in any species of crab.Bimodal ventilation of the branchial chambers occurs in stressed or active crabs partly immersed in shallow water. This consists of an alternation between forward water flow and reversed air flow.The morphology of the branchial chambers in Sudanonautes, and observational data on the patterns of ventilation of the branchial chambers, are discussed in relation to those described for other air-breathing decapod crustaceans.     

Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha

Although alpha(2)beta(1) integrin (glycoprotein Ia/IIa) has been established as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from the venom of Calloselasma rhodostoma, induces platelet activation that can be blocked by monoclonal antibodies against alpha(2)beta(1) integrin. This finding suggested that clustering of alpha(2)beta(1) integrin by rhodocytin is sufficient to induce platelet activation and led to the hypothesis that collagen may activate platelets by a similar mechanism. In contrast to these findings, we provided evidence that rhodocytin does not bind to alpha(2)beta(1) integrin. Here we show that the Cre/loxP-mediated loss of beta(1) integrin on mouse platelets has no effect on rhodocytin-induced platelet activation, excluding an essential role of alpha(2)beta(1) integrin in this process. Furthermore, proteolytic cleavage of the 45-kDa N-terminal domain of glycoprotein (GP) Ibalpha either on normal or on beta(1)-null platelets had no significant effect on rhodocytin-induced platelet activation. Moreover, mouse platelets lacking both alpha(2)beta(1) integrin and the activating collagen receptor GPVI responded normally to rhodocytin. Finally, even after additional proteolytic removal of the 45-kDa N-terminal domain of GPIbalpha rhodocytin induced aggregation of these platelets. These results demonstrate that rhodocytin induces platelet activation by mechanisms that are fundamentally different from those induced by collagen.     

2,2'-Bipyridinebutyldithiocarbamatoplatinum(II) and palladium(II) complexes: synthesis, characterization, cytotoxicity, and rich DNA-binding studies

Butyldithiocarbamate sodium salt (Bu-dtcNa) and its two complexes, [M(bpy)(Bu-dtc)]NO3 (M=Pt(II) or Pd(II) and bpy=2,2'-bipyridine), have been synthesized and characterized on the basis of elemental analysis, molar conductivities, IR, 1H NMR, and UV-vis spectra. In these complexes, the dithiocarbamato ligand coordinates to Pt(II) or Pd(II) center as bidentate with two sulfur atoms. These complexes show 50% cytotoxic concentration (Cc(50)) values against chronic myelogenous leukemia cell line, K562, much lower than that of cisplatin. The interaction of these complexes with calf thymus DNA was extensively investigated by a variety of spectroscopic techniques. These studies showed that both complexes presumably intercalate in DNA. UV-vis studies imply that they cooperatively bind with DNA and unexpectedly denature the DNA at very low concentrations (approximately 100 microL). Palladium complex breaks the DNA into two unequal fragments and binds stronger to the lighter fragment than to the heavier one. In the interaction studies between the Pt(II) and Pd(II) complexes with DNA, several binding and thermodynamic parameters have been determined, which may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids.     

Effect of starvation on copulatory activity of Ercolania nigra (Lemche, 1935) (Mollusca,Opisthobranchia, Ascoglossa)

Feeding dominates copulatory behavior in the few opisthobranchs for which behavioral hierarchies have been established. However, the influence of starvation on the dominant role has not been investigated previously. The present study investigates copulatory activity in the ascoglossan opisthobranch Ercolania nigra (Lemche) subject to varying starvation regimes. Copulatory activity of E. nigra is significantly higher in unstarved animals than in animals starved for 2h, 6h, and 24h. The decrease in copulatory activity is independent of the duration of previous starvation within the range tested (2–24 h). Copulatory behavior dominates feeding behavior in 60–80% of the cases, regardless of the duration of previous starvation. Thus the behavioral hierarchy of E. nigra differs markedly from that of the opisthobranchs previously investigated.     

Aminomalonato(1,2-diaminocyclohexane)platinum(II): A competitive antitumor compound within a new class of neutral,chemically stable,water soluble,functionalized platinum(II) complexes

Antitumor, neutral, chemically stable, water soluble and functionalized aminomalonato-platinum(II) complexes have been prepared and their mode of coordination characterized by elemental analysis and infrared spectra. Among this new class of compounds, aminomalonato(1,2-diaminocyclohexane)platinum(II) has been selected for ¹³C NMR measurements and for initial evaluation against L1210 and B 16 melanoma. The preliminary biological results reveal the high anti- neoplastic potential of this compound.     

Synthesis, characterization, antibacterial and cytotoxic study of platinum (IV) complexes

Platinum (IV) complexes [Pt (L)2Cl2] [where, L= benzyl-N-thiohydrazide (L1), (benzyl-N-thio)-1,3-propanediamine (L2), benzaldehyde-benzyl-N-thiohydrazone (L3) and salicylaldehyde-benzyl-N-thiohydrazone (L4)] have been synthesized. The thiohydrazide, thiodiamine and thiohydrazones can exist as thione-thiol tautomer and coordinate as a bidentate N-S ligand. The ligands were found to act in monobasic bidentate fashion. Analytical data reveal that metal to ligand stoichiometry is 1:2. The complexes have been characterized by elemental analysis, IR, mass, electronic and 1H NMR spectroscopic studies. In vitro antibacterial and cytotoxic studies have been carried out for some complexes. Various kinetic and thermodynamic parameters like order of reaction (n), activation energy (Ea), apparent activation entropy (S#) and heat of reaction (DeltaH) have also been carried out for some complexes.     

Synthesis,spectroscopic characterization,molecular docking and theoretical studies (DFT) of N-(4-aminophenylsulfonyl)-2-(4-isobutylphenyl) propanamide having potential enzyme inhibition applications

A mutual prodrug (1) of ibuprofen and sulphanilamide has been synthesized with dual activity and improved toxicity profile. The synthesized compound has been characterized by elemental analysis, FT-IR, ¹HNMR, ¹³CNMR and ESI-MS. The molecular geometry of the compound (1) was optimized using density functional theory (DFT/B3LYP) method with the 6-311G(d,p) basis sets in ground state. Geometric parameters (bond lengths, bond angles, torsion angles), vibrational assignments, chemical shifts and thermodynamics of the compound (1) has been calculated theoretically and compared with the experimental data. Comparative AutoDock study of compound (1) with cyclooxygenase enzymes (COX-1 and COX-2) were performed involving docking for possible selectivity of our prodrug within the two Cox enzymes. The highest binding affinities of −8.7 Kcal/mol and −8.1 Kcal/mol has been obtained for COX-1 and COX-2 enzymes respectively. Compound (1) exhibited enhanced anti-inflammatory, anti-ulcer and free radical scavenging activities as compared with the parent drugs. Based on various in vitro and in vivo tests it is suggested that the Compound (1) is more active than the parent drugs. Moreover, LD₅₀ of compound (1) is higher than parent drug i.e. ibuprofen and sulphanilamide suggesting that the synthesized compound is much safer than its parent analogous.     

The Spring-Run Ecotype of the Steelhead Trout Parasalmo (Oncorhynchus) mykiss (Walbaum, 1792) (Salmonidae,Salmoniformes) in the Kamchatka Peninsula

Russian Journal of Marine Biology - A seasonal spring-run (vernal) ecotype of the Steelhead Trout Parasalmo (Oncorhynchus) mykiss (Walbaum, 1792) has been found in western Kamchatka for the first...     

Epsilon subunit, an endogenous inhibitor of bacterial F(1)-ATPase, also inhibits F(0)F(1)-ATPase

Since the report by Sternweis and Smith (Sternweis, P. C., and Smith, J. B. (1980) Biochemistry 19, 526-531), the epsilon subunit, an endogenous inhibitor of bacterial F(1)-ATPase, has long been thought not to inhibit activity of the holo-enzyme, F(0)F(1)-ATPase. However, we report here that the epsilon subunit is exerting inhibition in F(0)F(1)-ATPase. We prepared a C-terminal half-truncated epsilon subunit (epsilon(DeltaC)) of the thermophilic Bacillus PS3 F(0)F(1)-ATPase and reconstituted F(1)- and F(0)F(1)-ATPase containing epsilon(DeltaC). Compared with F(1)- and F(0)F(1)-ATPase containing intact epsilon, those containing epsilon(DeltaC) showed uninhibited activity; severalfold higher rate of ATP hydrolysis at low ATP concentration and the start of ATP hydrolysis without an initial lag at high ATP concentration. The F(0)F(1)-ATPase containing epsilon(DeltaC) was capable of ATP-driven H(+) pumping. The time-course of pumping at low ATP concentration was faster than that by the F(0)F(1)-ATPase containing intact epsilon. Thus, the comparison with noninhibitory epsilon(DeltaC) mutant shed light on the inhibitory role of the intact epsilon subunit in F(0)F(1)-ATPase.