Ontogenetic features of <Emphasis Type="Italic">Dolichopithecus</Emphasis> (Primates,Colobidae) from the Pliocene of Pridnestrovie

In the permanent dentition of the extinct genus Dolichopithecus, M₁, I₁, and I₂ were the first to erupt, followed by M₂, canine, P₄, and P₃. M₃ was the last permanent tooth to erupt. At the stage of eruption of P₄ and P₃, M₃ was incompletely mineralized. The difference from the extant Cercopithecoidea is the loss of all deciduous teeth after eruption of incisors and M1 and the similarity is observed in the succession of eruption of permanent teeth. In Dolichopithecus, the lower jaw body retained constant in thickness after eruption of M₂. The lower jaw increased in length and depth, as the horizontal ramus grew with the formation and eruption of M₃.     

An adapid primate,sinoadapis, from lufeng,latest miocene,Yunnan, China

The paper deals with a new form ofSinoadapis from the Lufeng hominoid Locality, assigned toSinoadapis shihuibaensis sp. nov. Holotype PA 882 A fragment of right mandible with C,−M₃. Other materials. PA 903 A fragment of left maxilla with P³−M³. PA 959 Left lower tooth row with I₁−P², P₄. PA 902 Right upper tooth row with C′−P³. PA 964 An isolated left I¹. PA 907 An isolated right I³. PA 972 An isolated right M³.     

ATPase activity in plasmalemma-rich vesicles isolated by aqueous two-phase partitioning from Vicia faba mesophyll and epidermis: Characterization and influence of abscisic acid and fusicoccin

Plasmalemma-rich microsomal vesicles were prepared from whole leaf and acid-washed epidermal tissue of Vicia faba L. cv. Osnabrücker Markt by aqueous two-phase partitioning in dextran T-500 and polyethylenglycol 1350 aqueous phases. These vesicles were tightly sealed and predominantly right-side out, and contained a K⁺ -stimulated, mg²⁺-dependent and vanadate-sensitive ATPase. The enzyme from both tissues exhibited nearly identical properties: pH optimum 6.4, K_m for ATP 0.60 mM(whole leaf) and 0.67 mM (epidermis). V_max -480 nmol (mg protein)¹ min¹ (whole leaf) and 510 nmol (mg protein)¹ min¹ (epidermis), I₅₀ (Na₃,VO₄) 7.5 μM (whole leaf) and 15 μM (epidermis). The enzyme was not inhibited by NO₃(50 mM)or sodium azide (I mM). DCCD (20 μM) reduced enzyme activity to 50% (whole leaf) and 58% (epidermis), gramicidin S (20 μM) to 36% (whole leaf) and 41%(epidermis). Ca²⁺ inhibited the ATPase [I₅₀, C²⁺: 0.5 mM(whole leaf) and 0.8 mM(epidermis)]. Ca²⁺ inhibited the ATPase [I₅₀, C²⁺ 0.5 mM(whole leaf) und 0.8 (epidermis)]. The vanadate-sensitive ATPase from whole leaf and epidermal tissue was slightly but significantly stimulated by fusicoccin (FC) at a concentration (0.13 μM) promoting stomatal opening. The stimulation was not seen in the solubilized ATPase. Stomata of the cultivar used here were insensitive lo (±)ABA up to 2 μM level which is effective in most other cultivars and species. Likewise, at this concentration no effect of ABA on the activity of the epidermal ATPase was observed. The data are discussed with respect to the interaction of FC and ABA with the ATPase.     

Development of the orangutan permanent dentition: Assessing patterns and variation in tooth development

This study examines dental formation and alveolar emergence in a large cross-sectional sample composed primarily of wild-reared orangutans (N = 89) in order to provide information on the development of the permanent dentition in this hominoid and to address questions of variation in individual tooth formation, between teeth and between individuals. All specimens have been radiographed in lateral aspect and stages of crown and root formation recorded for all teeth. The ranges of crown and root formation of I¹₁, C¹₁, P⁴₄, and M³₃ have been calculated relative to the stage of M₁¹ development within a specific tooth quadrant. Then, for each specimen, BMDP scatterplot and nonparametric statistics have been used to graph changes in stages of these teeth relative to M¹₁ stages and to examine relationships between pairs of upper and lower dental counterparts and between teeth of each jaw. Results indicate 1) high correlations between upper and lower tooth pairs and between many of the permanent teeth within individuals, 2) a relatively large range of variability in individual tooth development (multistage ranges relative to M¹₁), 3) greater variation in root development at emergence than earlier reports, and 4) evidence of variability within the sequence emergence pattern of the orangutan. © 1996 Wiley-Liss, Inc.     

Effect of NH4 +:NO3 - ratios on growth and nitrogen uptake by onions

The modelling of ion uptake by plants requires the measurement of kinetic and growth parameters under specific conditions. The objective of this study was to evaluate the effect of nine NH _inf4 ^sup+ :NO _inf3 ^sup− ratios on onions (Allium cepa L.). Twenty-eight to 84 day-old onion plants were treated with NH _inf4 ^sup+ :NO_f3/sup− ratios ranging from 0 to 100% of each ionic species in one mM solutions in a growth chamber. Maximum N influx (I_max) was assessed using the N depletion method. Except at an early stage, ionic species did not influence significantly I_max, the Michaelis constant (K_m) and the minimum concentration for net uptake (C_min). I_max for ammonium decreased from 101 to 59 pmole cm^-2 s^-1 while I_max for nitrate increased from 26 to 54 pmole cm^-2 s^-1 as the plant matured. On average, K_m and C_min values were 14.29 μM, and 5.06 μM for ammonium, and 11.90 μM and 4.54 μM for nitrate, respectively. In general, the effect of NH₄ ⁺:NO₃ ^- ratios on root weight, shoot weight and total weight depended on plant age. At an early stage, maximum plant growth and N uptake were obtained with ammonium as the sole source of N. At later stages, maximum plant growth and N uptake were obtained as the proportion of nitrate increased in the nutrient solution. The was no apparent nutrient deficiency whatever NH₄ ⁺:NO₃ ^- ratio was applied, although ammonium reduced the uptake of cations and increased the uptake of phosphorus. The research was supported by the Natural Sciences and Engineering Research Council of Canada.     

Additional materials of Myanmarpithecus yarshensis (Amphipithecidae, Primates) from the middle Eocene Pondaung Formation

Myanmarpithecus yarshensis is an amphipithecid primate from the middle Eocene Pondaung Formation in Myanmar. It was previously known based on maxillary fragments with P⁴–M³ and mandibular fragments with C–P₃ and M_2–3. This study reports new materials for the genus, including a humeral head fragment, a lingual fragment of the right M², a lingual fragment of the right M³, and a left I¹. These new materials were collected from approximately the same point, and likely belonged to the same individual. The upper molar morphology and size of the new materials show similarity to those of the type specimen, indicating that the new materials can be assigned to M. yarshensis. The humeral head is the first postcranial element that is associated with dental materials for amphipithecids. The morphological similarity between the previously reported larger humerus and this specimen confirms the assignment of the former specimen to Amphipithecidae and suggests common locomotor adaptations in the family. The upper central incisor is large relative to the molar fragments, but is within the variation among extant platyrrhines. The tooth is spatulate-shaped and high crowned, and lacks the mesial process, indicating similarity to I¹ of haplorhines and clear differences from that of adapoids. It has been suggested that amphipithecids, including Myanmarpithecus, have affinities with notharctine adapoids, but the morphology of I¹ does not support the notharctine hypothesis of the Amphipithecidae.     

Dental characters of the Quaternary tapirs in China, their significance in classification and phylogenetic assessment

Most of the Quaternary tapir fossils from China are isolated teeth. The purpose of this paper is to identify them and to extract systematic and evolutionary information from them. Based on morphology and W/L ratio, isolated teeth can be identified successfully. On the whole, the identification of P¹, M³ and P₂ is believed to be reliable, while it is difficult to distinguish P₃ from P₄, M₁ from M₂ etc. Concerning the variations of the teeth, P¹ is the most variable one in dimension. In the Quaternary tapirs in China, some dental characters can be used as reliable indicators to evaluate their evolutionary levels. The degree of the atrophy of the upper canine relative to the caniniform I³ is reflected in the C/I³ diameter ratio, which is decreasing during evolution. P¹ changes considerably in outline and strength of the hypocone. Some forms are without hypocone, such as Tapirus sanyuanensis, some have a very faint hypocone, such as Tapirus indicus; although most of them show a developed hypocone. For other cheek teeth, the W/L ratio is decreasing through geologic time. Two lineages can be tentatively proposed: one is the Tapirus peii-Tapirus sinensis-Megatapirus augustus progression; the other is the T. sanyuanensis-T. indicus lineage. T. sanyuanensis and T. peii stand on the base, and it is very probable that the latter is more primitive.     

Photoecology of the coral Leptoseris fragilis in the Red Sea twilight zone (an experimental study by submersible)

Summary Depth-dependent photoadaptational responses of the Red Sea zooxanthellate coral (Leptoseris fragilis) were studied down to 160 m from the research submersible GEO. Light saturation curves for photosynthesis revealed, with I _C=1-2, I _K=10.9 and I _sat=20 E·cm^–2·sec^–1, the lowest values of photokinetic parameters ever reported for a symbiotic coral. In summer, positive net production occurs only around noon at approx. 100m depth. Biomass parameters of corals at 100–135 m are negatively correlated with depth in algal cell density, protein, chlorophyll and carotenoid but not in pigment ratios or cell based pigment content. Coral size decreased with depth. Corals transplanted from 110–120 m original depth to 40, 70, 90 and 160 m showed high survival after one year. O₂-production and dark O₂-uptake increased with decreasing transplantation depth. After one year, transplants at 70 and 90 m but not at 40 m had higher algae density and pigment concentrations. The host light-harvesting systems described by Schlichter, Fricke and Weber (1986) are partially destroyed in 40 m but not in 70 and 90 m transplants. Different light exposures alter P-I-responses (P _max, I _C, I _K, I _sat) but not biomass parameters, indicating molecular or biochemical adaptation. The coraal's optimal light fields lie between 70 to 90 m. Its exceptional bathymetric distribution is linked with the newly discovered host light-harvesting systems which probably enhance photosynthetic performance in a dim environment.     

Tooth Replacement in Late Jurassic Dryolestidae (Eupantotheria, Mammalia)

The discovery of juvenile dentitions of late Jurassic (Kimmeridgian) Dryolestidae (Eupantotheria, Mammalia) from Guimarota, Portugal, yields for the first time information on the mode of tooth replacement in therian mammals prior to the dichotomy of placentals and marsupials. As in extant placentals, tooth replacement occurs at all antemolar positions [incisors (I1–I4), canine (C), premolars (P1–P4)]. P1 and P2 have premolariform milk predecessors, whereas the large premolariform third (P3) and fourth premolars (P4) are preceded by molariform deciduous premolars (dP3, dP4). Tooth replacement takes place in two waves, at least in the lower jaw, with I₂, I₄, P₁, and P₃ in the first series and I₁, I₃, C, P₂, and P₄ in the second. P₄ is the last premolar to erupt, and it is present when the sixth molar (M₆) starts to break through. The reduced tooth replacement pattern of marsupials (with only dP3 being replaced postnatally) evolved secondarily from the primitive or plesiomorphic mammalian condition, which was retained in Dryolestidae and Eutheria.     

Studying the interaction between three synthesized heterocyclic sulfonamide compounds with hemoglobin by spectroscopy and molecular modeling techniques

The interaction between synthesized heterocyclic benzene sulfonamide compounds, N-(7-benzyl-56-biphenyl-2m-tolyl-7H-pyrrolo[23-d]pyrimidine–4–yl)-benzene sulfonamide (HBS₁), N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d] pyrimidine-4-yl)-4-methyl- benzene sulfonamide (HBS₂), and N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-4-chloro-benzene sulfonamide (HBS₃) with Hb was studied by fluorescence quenching, zeta potentional, circular dichroism, and molecular modeling techniques. The fluorescence spectroscopy experiments were performed in order to study the conformational changes, possibly due to a discrete reorganization of Trp residues during binding between HBS derivatives and Hb. The variation of the K_SV value suggested that hydrophobic and electrostatic interactions were the predominant intermolecular forces stabilizing the complex. The K_SV1 ans K_SV2 values of HBS derivatives with Hb are .6 × 10¹³ and 3 × 10¹³ M^?1 for Hb–HBS₁, 1 × 10¹³ and 4 × 10¹³ M^?1 for Hb–HBS₂, .9 × 10¹³, and 6 × 10¹³ M^?1 for Hb–HBS₃, respectively. The molecular distances between Hb and HBS derivatives in binary and ternary systems were estimated according to Förster’s theory of dipole–dipole non-radiation energy transfer. The quantitative analysis data of circular dichroism spectra demonstrated that the binding of the three HBS derivatives to Hb induced conformational changes in Hb. Changes in the zeta potential of the Hb–HBS derivatives complexes demonstrated a hydrophobic adsorption of the anionic ligand onto the surface of Hb as well as both electrostatic and hydrophobic adsorption in the case of the complex. The modeling data thus confirmed the experimental results. This study is expected to provide important insight into the interaction of Hb with three HBS derivatives to use in various toxicological and therapeutic processes.     

Analogs of host-specific phytotoxin produced by Helminthosporium maydis,race T: II. Biological activities

Inhibition of dark CO₂ fixation by susceptible corn leaves was used to compare the relative toxicity of synthetic analogs with that of the host-specific phytotoxin produced by the fungal corn pathogen, Helminthosporium maydis, race T. Analogs with C₁₅, C₂₅, or C₂₆ chain lengths and 1,5-dioxo-3-hydroxy functions were only slightly less toxic (2–6 × 10^?7M) than native T toxin (C₃₅–C₄₅ chain lengths) or its individual components (3 × 10^?8M). Like native toxin, analogs were host-specific in that they did not inhibit dark CO₂ fixation in leaf tissue of resistant corn at concentrations 10²–10³ times greater than those effective with susceptible corn. These findings support the structures previously proposed for native T toxin.     

Traumatic injury to the incisive bones and maxillary dentition in a male gray wolf (Canis lupus L.) from Slovakia

The paper presents the skull of a male gray wolf shot in the region of Snina, eastern Slovakia. Age at death of the wolf was estimated at 6 years. The skull was characterized by the almost-complete absence of the alveolar processes of the incisive bones and multiple dental abnormalities that were attributed to a severe trauma. All maxillary incisors and both maxillary first premolars were missing. In addition, both maxillary canines were fractured with only tooth fragments being left. The pulp exposure associated with the crown fractures of the maxillary canines had caused pulp necrosis and periapical lesions, as evidenced on radiographs. The right P², P³, and P⁴ were fractured, with only the remaining tooth structure of the second and third premolars being left. In the right P⁴ and the left M¹, periapical bone resorption was diagnosed radiologically. In the mandibular dentition, the right I₂ and left P₁ had been lost in life. The mandibular canines exhibited distinct wear facets that were caused by contact with the maxillary third incisors, which were subsequently lost. The fact that all fractured teeth showed signs of wear indicates that the trauma had occurred some time before the wolf was shot.     

The collapse of benthic macroalgal blooms in response to self‐shading

1. Our goal was to use physiological indicators [photosynthesis–irradiance (P–I) response, nutrient status], population level feedbacks (self‐shading) and ambient environmental conditions (dissolved nutrients, light, temperature) to improve our understanding of the seasonal and spatial population dynamics of Cladophora. 2. Cladophora grew in three distinct phases, rapid growth early in the season (May–July), a mid‐season population collapse (July–August) and autumn re‐growth. Across all sites and dates, mean net maximal photosynthesis [P_M (NET)] was 6.9 ± 3.9 mg O₂ g DM^?1 h^?1, and α was 0.055 ± 0.025 mg O₂ g DM^?1 μm photons^?1 m^?2. Mean values for critical irradiance (I_CR) and the half‐saturation light intensity (I_K), were 42.9 ± 32.1 and 189.3 ± 123.8 μm photons^?1 m^?2 s^?1 respectively. 3. At most sites growth was phosphorus‐limited. Values of α were significantly higher at a site influenced by a nutrient enriched river plume, where algal growth was phosphorus‐sufficient. 4. Photoinhibition was not apparent in any of our P–I experiments. Even if photoinhibition had been apparent during in vitro P–I experiments, population level photosynthetic rates in the field would be little affected because intense self‐shading restricts inhibiting irradiances to the upper few mm–cm of the algal canopy. 5. Our physiological (P–I response) experiments contradicted previous assertions that high ambient temperatures, or nutrient deficiency, were primary causes of mid‐summer sloughing. In our study, sloughing occurred simultaneously at nutrient enriched and nutrient deficient sites, at temperatures well below critical values found during in vitro experiments, and our indicator of physiological condition (P–I response) remained unchanged leading up to, or immediately after, the sloughing event. 6. Self‐shading can reduce the convexity of the P–I response within in vitro incubations, even when the amount of algal material is low. Our experiments used 0.08 g DM of algal material that formed clumps c. 1 cm thick. Under these conditions, we estimated negligible (<1%) effects on P_M, a 12% reduction in apparent values of α, and 14% and 17% increases in values of the α‐dependent terms I_CR and I_K, respectively. 7. Our results are consistent with the hypothesis that a population‐level negative feedback (self‐shading) is responsible for sloughing in dense macroalgal beds. Sloughing was probably inevitable once macroalgal bed density and thickness surpassed a critical threshold. Cells towards the base of the bed received insufficient light to maintain metabolic balance, began to decay and weaken, and became increasingly susceptible to physical detachment from shear stress.     

Purification and Characterization of β-N-Acetylhexosaminidase from the Liver Prawn,Penaeus japonicus

β-N-Acetvlhexosaminidase (EC 3.2.1.52) was purified from the liver of a prawn, Penaeus japonicus, by ammonium sulfate fractionation and chromatography with Sephadex G-100, hydroxylapatite, DEAE-Cellulofine, and Cellulofine GCL-2000-m. The purified enzyme showed a single band keeping the potential activity on both native PAGE and SDS–PAGE. The apparent molecular weight was 64,000 and 110,000 by SDS–PAGE and gel filtration, respectively. The pI was less than 3.2 by chromatofocusing. The aminoterminal amino acid sequence was NH₂-Thr-Leu-Pro-Pro-Pro-Trp-Gly-Trp-Ala-?-Asp-Gln-Gly-VaI-?-Val-Lys-Gly-Glu-Pro-. The optimum pH and temperature were 5.0 to 5.5 and 50°C, respectively. The enzyme was stable from pH 4 to 11, and below 55°C. It was 39% inhibited by 10mM HgCl₂.

Steady-state kinetic analysis was done with the purified enzyme using N-acetylchitooligosaccharides (GlcNAc_n, n = 2 to 6) and p-nitrophenyl N-acetylchitooligosaccharides (pNp-β-GlcNAc_n, n= 1 to 3) as the substrates. The enzyme hydrolyzed all of these substrates to release monomeric GlcNAc from the non-reducing end of the substrate. The parameters of K_m and k_cat at 25°C and pH 5.5 were 0.137 mM and 598s^–1 for pNp-β-GlcNAc, 0.117 mM and 298s^–1 for GlcNAc₂, 0.055 mM and 96.4s^–1 for GlcNAc₃, 0.044 mM and 30.1 s^–1 for GlcNAc_4, 0.045 mM and 14.7 s^–1 for GlcNAc₅, and 0.047 mM and 8.3 s^–1 for GlcNAc₆, respectively. These results suggest that this β-N-acetylhexosaminidase is an exo-type hydrolytic enzyme involved in chitin degradation, and prefers the shorter substrates.     

Synthesis of metal dithiolene complexes by Si–S bond cleavage of a bis(silanylsulfanyl)alkene

A new method for the synthesis of metal dithiolenes with alkyl-substituted chelate rings has been investigated. The utility of the protected ene-1,2-dithiolate 3,4-bis-triisopropylsilanyl-sulfanyl-hex-3-ene as a precursor in reactions with metal halide and oxyhalide complexes was examined. Reaction conditions involve a 2:1 or 3:1 mol ratio of reactants in acetonitrile/THF or toluene at 50–80 °C for 24–36 h. Complex formation was observed as a result of Si–S bond cleavage by bound or free halide and oxo ligands. Members of four major structural families of dithiolene complexes were prepared in ca. 25–70% yields, including planar [Ni(S₂C₂Et₂)₂], square pyramidal [MI(S₂C₂Et₂)₂] (M = Co, Fe), [Fe(py)(S₂C₂Et₂)₂]¹⁻, and [ReO(S₂C₂Et₂)₂]¹⁻, centrosymmetric [M₂(S₂C₂Et₂)₄]²⁻ (M = Co, Mn), [M(S₂C₂Et₂)₃]¹⁻ (M = V, Nb), and trigonal prismatic [M(S₂C₂Et₂)₃] (M = Mo, W). Seven X-ray structure proofs are provided. It is concluded that the method is feasible and potentially extendable to other ring substituents, whose primary effects are on solubility and modulation of redox potentials.     

HYBRIDS AND INDUCED AMPHIPLOIDS OF ELYMUS CANADENSIS X AGROPYRON LIBANOTICUM

North American Elymus canadensis L., 2n = 28, and Asian Agropyron libanoticum Hack., 2n = 14, crossed with ease and yielded vigorous but sterile F₁ hybrids, 2n = 21. Chromosome pairing in the hybrids averaged 9.47^I, 5.38^II, and 0.26^III in 150 metaphase-I cells. One genome of E. canadensis is more or less homologous with the A. libanoticum genome. Treatment of the F₁ hybrids with colchicine produced 42-chromosome amphiploids, C₀, which were advanced through two seed generations, C₁ and C₂. More than half of the metaphase-I cells in the C₀ amphiploids contained 21^II; and average associations were 1.09^I, 20.16^II, 0.07^III, and 0.09^IV in 116 cells. Meiosis became increasingly irregular beyond metaphase-I; nevertheless, the C₀ amphiploids produced 68% stainable pollen and averaged 0.75 seed per spikelet. Multivalent frequencies increased in advanced generations, and the C₂ amphiploids averaged 1.11^I, 19.00^II, 0.23^III, and 0.55^IV in 100 metaphase-I cells. Meiosis was essentially regular in the C₁ and C₂ amphiploids beyond metaphase I, and the C₂ amphiploids averaged 73% stainable pollen and 2.28 seeds per spikelet. The amphiploids have an excellent chance of developing into a meiotically stable, fertile, new species. Forage characteristics of the amphiploids indicate that they have considerable economic potential as a forage grass.     

Occlusal and morphogenetic field evolution in the dentition of European Nyctitheriidae (Euarchonta,Mammalia)

Abstract

The nyctithere genera Saturninia, Cryptotopos and members of the subfamily Amphidozotheriinae are well-represented by dental remains in the European later Eocene. Their molar occlusal relations are described in detail, demonstrating a diversity of adaptations to insectivory, including dilambdodonty, minor trends in zalambdodonty, development of a large talon shelf in upper first and second molars and a step in the trigon-trigonid shearing surface that provides an extra facet in buccal phase. Minor lingual phase wear is recognized for the first time in the family, but only in relatively worn teeth. Nyctithere molars differ from those of most insectivorous mammals today in having well-developed paraconules and metaconules on upper molars, which in most cases lack a marked bucco-lingual tilt, associated with a more transverse jaw action. Amphidozotherium, however, shows tilting and a basally shifted M¹ hypocone associated with M₁ talonid exodaenodonty and a minor trend in zalambdodonty. Nyctitheres primitively have three deeply notched lobate lower incisors and a large but procumbent premolariform lower canine. Amphidozotheriines have modified their I₃ into a premolariform tooth, by shifting the premolarization field mesially. Amphidozotherium has also shifted this field distally, reducing P_2–3 in size and their roots from two to one.     

New phenotypes of serum α 1-antitrypsin in Japanese detected by gel slab isoelectric focusing

Summary The phenotype distribution and gene frequencies of serum ₁-antitrypsin in 856 healthy blood donors in Tokyo were examined by gel slab isoelectric focusing (pH 4–6). The allele of the common subtype variant Pi M₂ was present with a frequency of 0.1099 in Japanese. A study of 23 twin pairs and their parents was in agreement with the hypothesis of autosomal codominant inheritance of Pi M subtypes. Other rare variant alleles, Pi M^F, Pi M^S, Pi M^N, Pi M^V, Pi M^X, Pi M^Z were found in very low frequencies.The total concentration of serum ₁-antitrypsin was compared among three different phenotypic groups (M₁, M₁M₂, M₂). Statistically significant quantitative differences were found among these three groups (P<0.01).     

An insight to the dynamics of conserved water-mediated salt bridge interaction and interdomain recognition in hIMPDH isoforms

Inosine monophosphate dehydrogenase (IMPDH) is involved in de novo biosynthesis pathway of guanosine nucleotide. Type II isoform of this enzyme is selectively upregulated in lymphocytes and chronic myelogenous leukemia (CML) cells, and is an excellent target for antileukemic agent. The molecular dynamics simulation results (15?ns) of three unliganded 1B3O, 1JCN, and 1JR1 structures have clearly revealed that I_N, I_C (N- and C-terminal of catalytic domains) and C₁, C₂ (cystathionine-beta-synthase-1 and 2) domains of IMPDH enzyme have been stabilized by six conserved water (center) mediated salt bridge interactions. These conserved water molecules could be involved in interdomain or intradomain recognition, intradomain coupling, and charge transfer processes. The binding propensity of cystathionine-beta-synthase domain to catalytic domain (through conserved water-mediated salt bridges) has provided a new insight to the biochemistry of IMPDH. Stereospecific interaction of I_N with C₂ domain through conserved water molecule (K109–W^II ₁–D215/D216) is observed to be unique in the simulated structure of hIMPDH-II. The geometrical/structural consequences and topological feature around the W^II ₁ water center may be utilized for isoform specific inhibitor design for CML cancer.

An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:1     

New antitumor titanocene derivatives containing hydrophilic ligands

Four titanocene derivatives containing hydrophilic ligands were tested for antiproliferative activity against Ehrlich ascites tumor in mice. The new compounds (C₅H₅)₂TiCl(p-SC₆H₄NH₃⁺Cl^?) (I) and (C₅H₅)₂Ti(p-SC₆H₄NH₃⁺Cl^?)₂ (II), containing hydrochlorinated p-aminothiophenolate ligands, and the known compounds (C₅H₅)₂Ti(cis-OOCCHCHCOOH)₂ (III) and (C₅H₅)₂Ti(OOCCCl₃)₂ (IV) containing the carboxylic acid anions hydrogen- maleinate and trichloroacetate as acido ligands, induced maximum cure rates of 100%. The T.I. values amounted to 4.4–4.6 (I), 3.5–4.1 (II), 3.7– 3.8 (III) and 5.5 (IV), and were slightly increased in comparison to (C₅H₅)₂TiCl₂ (T.I. = 3.3). The complexes I–III were rather soluble in water and equally active in a DMSO/saline (1/9, v/v) mixture, in pure saline and in buffered solutions. In the case of IV, the toxicity was considerably low (LD₅₀,440 mg/kg; LD₁₀₀, 500 mg/kg) in relation to (C₅H₅)₂TiCl₂ (LD₅₀, 100 mg/kg; LD₁₀₀, 140 mg/kg).