Preparation and characterization of a novel polymorph of indiplon, Form α

A new polymorph α of indiplon was discovered, initially prepared by two methods, and further characterized by various means including single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), variable temperature powder X-ray diffraction (VT-PXRD), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), Fourier transform Raman (FT-Raman) spectroscopy and solubility determination. The crystal structure of Form α as analyzed by SCXRD differ from the three previously reported polymorphs, Form I, II, and III. In addition, PXRD and solubility measurements could clearly distinguish between Form α and Form I. Slight differences between the two forms were also detected by FT-Raman. No differences between Form α and I were observed by DSC, which was explained by VT-PXRD results showing a solid-solid phase change from Form α to Form I during the heating process. Solubility measurements at various temperatures showed that the two polymorphs were mutually monotropic and that Form I was the relatively thermodynamically stable crystal form.     

Effect of the Form of Mineral Nitrogen on the Growth and Heterotrophic Fixation of 14С-Bicarbonate in Chlamydomonas reinhardtii

Russian Journal of Plant Physiology - The earlier-detected effect of the mineral nitrogen form in the nutrient medium (ammonium or nitrate) on the quantity of ribosomes in the cells of...     

Review of the fauna of Rotatoria,Cladocera, and Copepoda of the basin of the Anadyr’ River

The zooplankton composition is studied in the thermokarst, glacial and meteorite lakes, channels, former riverbeds, and hollows in the basin of Anadyr’. We found 174 taxa: 78, Rotatoria, 55, Cladocera, and 41, Copepoda. The most diverse is the lake fauna: 51 taxa of Rotatoria, 48, Cladocera, and 37, Copepoda. The thermokarst Lake Maiorskoe hosts 68 taxa: 31, Rotatoria, 14, Cladocera, and 23, Copepoda, wheras the cold ultraoligotrophic Lake El’gygytgyn features only one species of Cyclop of the group scutifer Cyclops neymanae Strel., and Rotatoria and Cladocera are present as allochtonous forms. The Copepoda illustrate the relations of the Anadyr’ fauna with those of Europe, North America, and Japan.     

Influence of β-cyclodextrin on the Properties of Norfloxacin Form A

Cyclodextrins are able to form host–guest complexes with hydrophobic molecules to result in the formation of inclusion complexes. The complex formation between norfloxacin form A and β-cyclodextrin was studied by exploring its structure affinity relationship in an aqueous solution and in the solid state. Kneading, freeze-drying, and physical mixture methods were employed to prepare solid complexes of norfloxacin and β-cyclodextrin. The solubility of norfloxacin significantly increased upon complexation with β-cyclodextrin as demonstrated by a solubility isotherm of the A_L type along with the results of an intrinsic dissolution study. The complexes were also characterized in the solid stated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffractometry, scanning electron microscopy (SEM), and solid-state nuclear magnetic resonance (ssNMR) spectrometry. The thermal analysis showed that the thermal stability of the drug is enhanced in the presence of β-cyclodextrin. Finally, the microbiological studies showed that the complexes have better potency when compared with pure drug.KEY WORDS: bioassay, complexation, intrinsic dissolution, norfloxacin, β-cyclodextrin     

Polydomy and the organization of foraging in a colony of the Malaysian giant ant Camponotus gigas (Hym. / Form.)

In Kinabalu National Park, Borneo we observed four colonies of the Malaysian giant ant Camponotus gigas in a primary forest. These predominantly nocturnal ants have underground nests, but forage in huge three-dimensional territories in the rain forest canopies. The colony on which our study was mainly focused had 17 nests with about 7000 foragers and occupied a territory of 0.8 ha. To improve observation and manipulation possibilities, these nests were linked at ground level by 430 m of artificial bamboo trail. A group of specialist transport worker ants carried food from `source' nests at the periphery to the central `sink' nest of the queen. Transport of food between nests started immediately after the evening exodus of the foragers. Transporter ants formed a physical subcaste among the minors and behaved according to predictions of the central-place foraging theory. Their load size was about five times that of the average forager and grew proportionally with head width. Longer distances were run by ants with greater head width and larger gross weight. Transporter ants that ran more often took heavier loads. Experiments with extra-large baits revealed that C. gigas used long-range recruitment to bring foragers from different nests to “bonanzas” at far distant places. The foraging strategy of C. gigas is based on a polydomous colony structure in combination with efficient communication, ergonomic optimization, polyethism and an effective recruitment system. Received: 16 March 1998 / Accepted: 24 August 1998     

Flexibility in the order of action and in the enzymology of the nuclease, polymerases, and ligase of vertebrate non-homologous DNA end joining： relevance to cancer, aging, and the immune system

Nonhomologous DNA end joining （NHEJ） is the primary pathway for repair of double-strand DNA breaks in human cells and in multicellular eukaryotes. The causes of double-strand breaks often fragment the DNA at the site of damage, resulting in the loss of information there. NHEJ does not restore the lost information and may resect additional nucleotides during the repair process. The ability to repair a wide range of overhang and damage configurations reflects the flexibility of the nuclease, polymerases, and ligase of NHEJ. The flexibility of the individual components also explains the large number of ways in which NHEJ can repair any given pair of DNA ends. The loss of information locally at sites of NHEJ repair may contribute to cancer and aging, but the action by NHEJ ensures that entire segments of chromosomes are not lost.     

How Small Are the Smallest Selectable Domains of Form?

Two lines of Drosophila melanogaster from the same base population were selected in opposite directions to produce simultaneous antagonistic changes in two very small (less than 0.2 mm) and closely adjacent (less than 0.3 mm) dimensions within the base of the wing. Wing dimensions near the targeted area became differentiated by large positive and negative percentage differences, while only small homogeneous percentage changes occurred in the remainder of the wing. If very small regions of morphology (less than 100 cells across) can respond to selection almost independently, even in small population samples, then the control of developmental detail must involve many genes, and the diversity of possible outcomes in development and adaptation must be large.     

Chemotaxis of the unicellular green algaDunaliella salina and the ciliatedTetrahymena pyriformis—effects of glycine,lysine, and alanine,and their oligopeptides

Chemotactic properties of amino acids (L-alanine, glycine and L-lysine) and their oligopeptides (10^–6M) and binding sites to these ligands were investigated in two unicellular models, the heterotrophicTetrahymena pyriformis and the auxotrophicDunaliella salina. Chemotaxis ofDunaliella induced by simple amino acids and their derivatives demonstrated that binding sites (receptors) for food molecules are not only present in the membrane but are also able to induce their basic physiological response. InTetrahymena, substances with special molecular structure and properties (polar, hydrophilic character of the signal peptide chain)-5-L-Lys, 5-Glywere required for chemoattraction, other peptides tested, lacking the required structure, were repellent. Divergences in chemotaxis and binding assays of both species suggest that trends of functional and binding parameters do not run parallel at this level of evolution.     

Cloning,characterisation and expression of the α-tubulin genes of the leech,Hirudo medicinalis

We have isolated two α-tubulin cDNAs from the leech, Hirudo medicinalis. Both encode putative proteins of 451 amino-acids which differ from each other at only two positions. Southern blotting suggests that there are only two α-tubulin genes in the leech. The genes contain two introns and, because of the extremely high homology of the nucleotide sequence from the second intron to the end of the genes, we have inferred that a gene conversion event about 9.5 million years ago has homogenised the Hirudo α-tubulin sequences. Using in situ hybridisation to tissue sections, we have shown that the two genes are probably expressed in all neurons of the leech ganglia and that their spatial distribution remains unchanged during neuronal regeneration. The deduced amino-acid sequences of the leech α-tubulins show that they have greatest similarity to those from a platyhelminth, echiuran and mollusc with rather less to arthropod α-tubulins. The protein sequences of the leech α-tubulins have been compared with representatives of those from across all phyla to determine if any specific feature labels certain isotypes of tubulin for neuronal expression.     

Assay, purification, properties and mechanism of action of γ-glutamylcysteine synthetase from the liver of the rat and Xenopus laevis

1. An improved radioassay for glutathione synthetase and gamma-glutamylcysteine synthetase was developed. 2. Xenopus laevis liver gamma-glutamylcysteine synthetase was purified 324-fold by saline-bicarbonate extraction, protamine sulphate precipitation, CM-cellulose and DEAE-cellulose column chromatography, and gel filtration. 3. Rat liver gamma-glutamylcysteine synthetase was purified 11400-fold by a procedure similar to that employed for the Xenopus laevis enzyme. 4. Rat liver gamma-glutamylcysteine synthetase activity was inhibited by GSH and activated by glycine. These effects, which were not found in the enzyme from Xenopus laevis, may have a regulatory significance. 5. Isotope-exchange experiments revealed fundamental differences in the partial reactions catalysed by the rat and Xenopus laevis synthetases. The enzyme from Xenopus laevis appears to follow a Bi Bi Uni Uni Ping Pong mechanism, with glutamyl-enzyme as intermediate before the addition of cysteine and the release of gamma-glutamylcysteine. The results for the rat liver enzyme are consistent with a Tri Tri sequential mechanism.     

X-Ray Structures of the LXRα LBD in Its Homodimeric Form and Implications for Heterodimer Signaling

Liver X receptors (LXRs) are nuclear receptors that are central regulators of cholesterol homeostasis, and synthetic LXR agonists have shown promise as promoters of reverse cholesterol transport and anti-inflammatory agents. Here, we present three X-ray structures of three different agonists bound to the ligand binding domain of LXRα. These compounds are GW3965, F₃methylAA, and a benzisoxazole urea, and we show that these diverse chemical scaffolds address common structural themes, leading to high binding affinity for LXR. Our structures show the LXRα ligand binding domain in its homodimeric form, an arrangement previously thought to be stereochemically difficult. A comparison with existing structures of the LXRβ homodimer and LXRα:RXR (retinoid X receptor) heterodimers explains differences in dimer affinity and leads us to propose a model for allosteric activation in nuclear receptor dimers, in which an unactivated RXR partner provides an inhibitory tail wrap to the cofactor binding pocket of LXR.     

Chitinozoan zonation of the Late Ordovician and the Early Silurian of the island of Anticosti, Québec, Canada

A reappraisal of chitinozoan distribution across the Ordovician-Silurian boundary on the Island of Anticosti has led to the recognition of a new zone, the Ancyrochitina ellisbayensis biozone, in the uppermost part of the Ellis Bay Formation. This biozone lies between the well defined Upper Ordovician Spinachitina taugourdeaui biozone and the lowest Silurian (Rhuddanian) Plectochitina nodifera biozone of the Becscie Formation. The occurrence of such diagnostic species as P. nodifera, Belonechitina postrobusta, Conochitina electa and Ancyrochitina ramosaspina in the Lower Silurian of Anticosti points to a close similarity to faunas in Estonia and north Latvia and indicates an age ranging from the Parakidograptus acuminatus to the Coronograptus cyphus in terms of graptolite zones. The chitinozoan biozonation harmonizes with that based on conodonts and, to a lesser extent, with the known graptolite faunal succession. Five new species: Ancyrochitina ellisbayensis sp. nov., Clathrochitina postconcinna sp. nov., Conochitina gunriveris sp. nov., Clathrochitina perexilis sp. nov., Bursachitina basiconcava sp. nov. and three species in open nomenclature are described.     

The composition,structure, and dynamics of the nekton of the upper epipelagic layer in the Aleutian and Commander basins,western Bering Sea,in the fall seasons of 2002–2013

The data on the composition and abundance of nekton species and their interannual variations within the upper epipelagic layer (0–50 m) in the Aleutian and Commander basins in the western Bering Sea that are considered in the article were collected during complex surveys that were conducted by the Pacific Research Fisheries Center in September and October of 2002–2013. The core species structures of the nekton communities in these two areas were similar: the chum salmon Oncorhynchus keta and the boreopacific gonate squid Boreoteuthis borealis were the most abundant species. Simpson’s dominance index varied synchronously in both areas, with higher values in the Aleutian Basin, until 2009. In the subsequent years, the values of the index for the studied areas became equal and varied asynchronously. An analysis of abundance showed that two types of species structure most often prevailed (with the dominance of either chum salmon or squid); in some years the species structure differed from that in other years. Species of the low-boreal and low-boreal-subtropical complexes were more abundant in the Commander Basin, reaching particularly high proportions in 2006, 2008, and 2012. Certain species showed similarity in the year-to-year dynamics of their abundance; however, these coincidences were frequently accidental. After the climate regime shift in 2006–2007, the total biomass of nekton in the Aleutian Basin decreased from 3241 to 1736 kg/km² (46%); in the Komandorskiye Basin it decreased from 2459 to 1976 kg/km² (20%).     

Comparative Study of the Absorption,Plasma Levels,and Urinary Excretion of the “New” and the “Old” Lanoxin

A comparative study was performed of the absorption, the plasma level at equilibrium, and the urinary excretion of digoxin using two types of Lanoxin tablets, those produced before and after the 1972 alteration of the tablet manufacture.After a single dose the absorption rate of the new tablets was about twice as great as the old, both in young subjects and in the elderly patients. There were no significant differences in the plasma levels of digoxin for the two tablets 15 hours after the last administration in patients on an equal maintenance dose. The urinary excretion of digoxin increased about 40% when the “old” Lanoxin was replaced by the “new.” In elderly patients a daily dose of 0·125 mg twice daily of the new tablets should be sufficient to reach the therapeutic range. Young people need a higher dosage. If the kidney function is reduced by as much as 50% the dose should be reduced.     

Preassembly and ligand-induced restructuring of the chains of the IFN-γ receptor complex： the roles of Jak kinases, Statl and the receptor chains

We previously demonstrated using noninvasive technologies that the interferon-gamma （IFN-γ） receptor complex is preassembled [ 1 ]. In this report we determined how the receptor complex is preassembled and how the ligand-mediated conformational changes occur. The interaction of Statl with IFN-γR1 results in a conformational change localized to IFN- γR1. Jakl but not Jak2 is required for the two chains of the IFN-γ receptor complex （IFN-γR1 and IFN-γR2） to interact; however, the presence of both Jakl and Jak2 is required to see any ligand-dependant conformational change. Two IFN- γR2 chains interact through species-specific determinants in their extracellular domains. Finally, these determinants also participate in the interaction of IFN-γR2 with IFN-γR1. These results agree with a detailed model of the IFN-γ receptor that requires the receptor chains to be pre-associated constitutively for the receptor to be active.     

Effects of the ΔF508 mutation on the structure,function, and folding of the first nucleotide-binding domain of CFTR

The fatal autosomal recessive disease cystic fibrosis (CF) is caused by mutations in the gene which encodes the cystic fibrosis transmembrane conductance regulator (CFTR). Many of these disease-causing mutations, including the deletion of F508 (F508) which accounts for approximately 70% of the disease alleles, occur in one of the two consensus nucleotide binding sequences. Peptide studies have directly demonstrated that the N-terminal nucleotide binding sequences bind adenine nucleotides. Structurally, circular dichroism spectropolarimetry indicates that this region of CFTR assumes a -stranded structure in solution. The F508 mutation causes a diminution in the amount of -stranded structure and a concomitant increase in the amount of random coil structure present, indicating that either the mutant peptide has a different native structure or that the conformational equilibrium is shifted toward a more disordered form. Furthermore, the mutant peptide is more sensitive to denaturation, indicating that F508 is a stability, or protein-folding mutant. Here we review these results and discuss their implications for interpreting the behavior of F508in situ and for the rational design of new CF drugs.     

β-decay,Bremsstrahlen, and the origin of molecular chirality

Summary A brief review is presented of the Vester-Ulbricht -decay Bremsstrahlen hypothesis for the origin of optical activity, and of subsequent experiments designed to test it. Certain of our experiments along these lines, begun in 1974 and involving the irradiation of racemic and optically active amino acids in a 61.7 KCi⁹⁰Sr–⁹⁰Y Bremsstrahlen source, have now been completed and are described. After 10.89 years of irradiation with a total Bremsstrahlen dose of 2.5×10⁹ rads, crystallinedl-leucine, norleucine, and norvaline suffered 47.2, 33.6, and 27.4% radiolysis, respectively, but showed no evidence whatsoever of asymmetric degradation.d- andl-Leucine underwent about 48% radiolysis and showed 2.4–2.9% radioracemization. Other samples in solution were too severely degraded to analyze. Probable intrinsic reasons for the failure of the Vester-Ulbricht mechanism to afford asymmetric radiolysis in the present and related experiments involving -decay Bremsstrahlen are enumerated.A portion of this material was presented at the 7th International Conference on the Origins of Life, Mainz, FRG, July 10–15, 1983     

Form–meaning links in the development of visual word recognition

Learning to read takes time and it requires explicit instruction. Three decades of research has taught us a good deal about how children learn about the links between orthography and phonology during word reading development. However, we have learned less about the links that children build between orthographic form and meaning. This is surprising given that the goal of reading development must be for children to develop an orthographic system that allows meanings to be accessed quickly, reliably and efficiently from orthography. This review considers whether meaning-related information is used when children read words aloud, and asks what we know about how and when children make connections between form and meaning during the course of reading development.