KinImmerse: Macromolecular VR for NMR ensembles

Background  

In molecular applications, virtual reality (VR) and immersive virtual environments have generally been used and valued for the visual and interactive experience – to enhance intuition and communicate excitement – rather than as part of the actual research process. In contrast, this work develops a software infrastructure for research use and illustrates such use on a specific case.     

Possible dynamic anchor points in a benzoxazinone derivative–human oxytocin receptor system — a molecular docking and dynamics calculation

In this study, we performed a molecular docking and dynamics simulation for a benzoxazinone–human oxytocin receptor system to determine the possible hydrophobic and electrostatic interaction points in the dynamic complex. After the homology modeling, the ligand was docked into the putative active using AutoDock 3.05. After the application of energetic and structural filters, the complexes obtained were further refined with a simulated annealing protocol (AMBER8) to remove steric clashes. Three complexes were selected for subjection to the molecular dynamics simulation (5 ns), and the results on the occurrence of average anchor points showed a stable complex between the benzoxazinone derivative and the receptor. The complex could be used as a good starting point for further analysis with site-directed mutagenesis, or further computational research. Figure The location of the ligands (complex B – blue; complex E – red; and complex F – green) in the transmembrane regions (TM1 – red; TM2 – blue; TM3 – yellow; TM4 – purple; TM5 – orange; TM6 – cyan; TM7 – pink) of the hOTR. For clarity, the EC and IC loops are not shown Electronic Supplementary Material Supplementary material is available at     

Progression age enhanced backward bifurcation in an epidemic model with super-infection

 We consider a model for a disease with a progressing and a quiescent exposed class and variable susceptibility to super-infection. The model exhibits backward bifurcations under certain conditions, which allow for both stable and unstable endemic states when the basic reproduction number is smaller than one. Received: 11 October 2001 / Revised version: 17 September 2002 / Published online: 17 January 2003 Present address: Department of Biological Statistics and Computational Biology, 434 Warren Hall, Cornell University, Ithaca, NY 14853-7801 This author was visiting Arizona State University when most of the research was done. Research partially supported by NSF grant DMS-0137687. This author's research was partially supported by NSF grant DMS-9706787. Key words or phrases: Backward bifurcation – Multiple endemic equilibria – Alternating stability – Break-point density – Super-infection – Dose-dependent latent period – Progressive and quiescent latent stages – Progression age structure – Threshold type disease activation – Operator semigroups – Hille-Yosida operators – Dynamical systems – Persistence – Global compact attractor     

Evolutionary Morphology in Belgium

In historical literature, Edouard van Beneden (1846–1910) is mostly remembered for his cytological discoveries. Less well known, however, is that he also introduced evolutionary morphology – and indeed evolutionary theory as such – in the Belgian academic world. The introduction of this research programme cannot be understood without taking both the international and the national context into account. It was clearly the German example of the Jena University that inspired van Beneden in his research interests. The actual launch of evolutionary morphology at his University of Liège was, however, also connected with the dynamic of Belgian university reforms and the local rationale of creating a research “school.” Thanks to his networks, his mastering of the rhetoric of the “new” biology, his low ideological profile and his capitalising on the new academic élan in late-19th century Belgium, van Beneden managed to turn his programme into a local success from the 1870s onwards. Two decades later, however, the conceptual underpinnings of evolutionary morphology came under attack and the “Van Beneden School” lost much of its vitality. Despite this, van Beneden’s evolutionary morphology was prototypical for the research that was to come. He was one of the first scientific heavyweights in Belgium to turn the university laboratory into a centre of scientific practice and the hub of a research school.     

Flax seed lignan in disease prevention and health promotion

Lignans have been part of both diet and herbal medicines for centuries. It is only in the last half century that phytochemists have described the structures of the lignans. Pharmacologists have only become interested in the biological activity of lignans in the last few decades. Much of the early interest focused on podophyllotoxin type lignans and their derivatives. Recent literature has recorded very many new lignans or lignan derivatives with a diverse range of biological activities. In 1955, the isolation from flax seed and the structure of the lignan derivative secoisolariciresinol diglucoside (SDG) was reported. Possible biological activity of SDG, and the mammalian lignan metabolites, enterolactone and enterodiol, was initially reported about 20 years later. During the next 30 years, there has been extensive research on the biological effects of both flax seed and rye lignans since both are metabolized into the mammalian lignans. Research on the activity of lignans on breast, colon, prostate and thyroid cancer has generally shown beneficial effects although there are some studies with either no conclusive or negative effect. Lignans have been shown to have positive effects in lowering relative risk factors for heart disease. Use of flax seed or SDG has been shown to have positive effects in both lupus and polycystic kidney disease models. Studies of both type I and II diabetes models have reported positive results when using SDG. Flax seed has also been reported to be hepatoprotective. Reproductive effects have been observed with flax seed or SDG and have been found to be dose and time related. There are many possible mechanistic explanations for the observed bioactivities including involvement in hormonal metabolism or availability, angiogenesis, anti-oxidation and gene suppression. Abbreviations: ALA – alpha linolenic acid; ApcMin – adenomatous polyposis coli multiple intestinal neoplasia; BBdp – BioBreeding diabetic prone; CCl₄– carbon tetrachloride; CDC – Crop Development Centre; CHD – cardiovascular heart disease; DMBA – dimethylbenzanthracene; DNA – deoxyribonucleic acid; ER – estrogen receptor; λGT –γ-glutamyltranspeptidase; HDL – high-density lipoprotein; HMGA – hydroxymethyl glutaric acid; IDDM – insulin dependent diabetes mellitus; LDL – low-density lipoprotein; MRL/lpr, Murine Lupus/lymphoproliferative; MDA – malondiadehyde; NIDDM – non-insulin dependent diabetes mellitus; ORF – oxygen free radical; PAF – platelet activating factor; PKD – Polycystic kidney disease; PEPCK – phosphoenolpyruvate carboxykinase; PMNL – polymorphonuclear monocytes; STZ – streptozoticin; TC – total cholesterol; TG – triglycerides; SDG – secoisolariciresinol diglucoside; ZDF – Zucker diabetic fatty. This revised version was published online in June 2006 with corrections to the Cover Date.     

ROS-Mediated ABA Signaling

In plants, reactive oxygen species (ROS) are short-lived molecules produced through various cellular mechanisms in response to biotic and abiotic stimuli. ROS function as second messengers for hormone signaling, development, oxygen deprivation, programmed cell death, and plant–pathogen interactions. Recent research on ROS-mediated responses has produced stimulating findings such as the specific sources of ROS production, molecular elements that work in ROS-mediated signaling and homeostasis, and a ROS-regulated gene network (Neill et al., Curr Opin Plant Biol 5:388–395, 2002a; Apel and Hirt, Annu Rev Plant Biol 55:373–399, 2004; Mittler et al., Trends Plant Sci 9:490–498, 2004; Mori and Schroeder, Plant Physiol 135:702–708, 2004; Kwak et al., Plant Physiol 141:323–329, 2006; Torres et al., Plant Physiol 141:373–378, 2006; Miller et al., Physiol Plant 133:481–489, 2008). In this review, we highlight new discoveries in ROS-mediated abscisic acid (ABA) signaling. Drs. Daeshik Cho and June M. Kwak are the corresponding authors for this paper.     

Multiple stochastic correlations among some cranioscopic traits

The traditional cranioscopic traits possess undoubted taxonomic value in interpreting interpopulational relationships. However, there is a lack of studies on the correlations between particular traits. In order to fill this gap, the following set of 4 traits was analysed by use of the multiple stachastic correlations method of Wanke: 1. prominence of maxilla, 2. lower margin of nasal aperture, 3. depth of canine fossa and 4. depth of maxillary incisure. These traits were examined by use of the photographic scales of Michalski within the series of 104 crania from a local population of Wislica, Poland, dated to the Early Medieval Period. The significant associations appeared in the combinations 1–2, 1–3, 3–4, 1–2–3, 1–2–4, 1–3–4, 2–3–4 and 1–2–3–4. After removal of all the possible interactions, still significant associations remained in 1–2–4, 2–3–4, and 1–3–4. Moreover, the places of significant surpluses appeared in the extreme places, i.e. those characterising the Europoid and Mongoloid crania.     

Development of a bioreactor system using an immobilized white rot fungus for decolorization

In this research the wood-rotting fungus Phanerochaete chrysosporium culture was shown to be immobilized very well on the porous foam material. The biomass concentration increased to about 2–3 g/l in 4–5 days. Repeated-batch decolorization tests using immobilized Phanerochaete chrysosporium cells were conducted for 16 days with initial concentrations of 50–500 ppm of Red 533 dispersed dye, a decolorization efficiency of 80% or higher was achieved within a period of one or two days. The ability of the immobilized culture to perform a long-term decolorization operation was confirmed. The authors wish to thank I.T.R.I. and the National Science Council of R.O.C. for financial supports.     

Intense cold and mortality in Castile-La Mancha (Spain): study of mortality trigger thresholds from 1975 to 2003

Studies on temperature–mortality time trends especially address heat, so that any contribution on the subject of cold is necessarily of interest. This study describes the modification of the lagged effects of cold on mortality in Castile-La Mancha from 1975 to 2003, with the novelty of also approaching this aspect in terms of mortality trigger thresholds. Cross-correlation functions (CCFs) were thus established with 15 lags, after application of ARIMA models to the mortality data and minimum daily temperatures (from November to March), and the results for the periods 1975–1984, 1985–1994 and 1995–2003 were then compared. In addition, daily mortality residuals for the periods 1975–1989 and 1990–2003 were related to minimum temperatures grouped in 2°C intervals, with a cold threshold temperature being obtained in cases where such residuals increased significantly (p < 0.05) with respect to the mean for the study period. A cold-related mortality trigger threshold of −3°C was obtained for Ciudad Real for the period 1990–2003. The significant number of lags (p < 0.05) in the CCFs declined every 10 years in Toledo (5–2–0), Cuenca (4–2–0), Albacete (4–3–0) and Ciudad Real (3–2–1). This meant that, while the trend in cold-related mortality trigger thresholds in the region could not be ascertained, it was possible to establish a reduction in the lagged effects of cold on mortality, attributable to the improvement in socio-economic conditions over the study period. Evidence was shown of the effects of cold on mortality, a finding that renders the adoption of preventive measures advisable in any case where intense cold is forecast.     

Preparation, Characterization and Evaluation of Marsupsin–Phospholipid Complex

The aim of this research was to formulate Marsupsin–phospholipid complex (M–P Complex) in attempt to increase the bioavailability of marsupsin and to characterize this new formulation along with its evaluation. Marsupsin–phospholipid complex was formulated by mechanical dispersion method. In this new formulation, complex formation was confirmed by carrying out transmission electron microscopy (TEM), IR, ¹H-NMR and RP-HPLC analysis. TEM showed M–P Complex diameter range of 0.05–0.5 μm. The entrapment efficiency of M–P Complex was found to be 44%. In vitro release study revealed its first order release profile. Mean blood serum concentration vs time curve of marsupsin was of first order after oral administration of M–P Complex in albino rabbits which clearly showed remarkably increased bioavailability of M–P Complex than standardized marsupsin. The average value of C _max and T _max of M–P Complex were found to be 3.02 mg/ml and 10.2 h, respectively. Hence the findings demonstrate that complexing marsupsin with phospholipids results in better oral bioavailability and improved biological response than free form of standardized marsupsin.     

Winter distribution of harp seals (Phoca groenlandica) off eastern Newfoundland and southern Labrador

The winter distribution of Newfoundland harp seals (Phoca groenlandica) was determined using sighting data collected during January and February from 1991 to 1995 aboard research vessels that covered the northeastern continental shelf between 46–55°N and 47–54°W. Data were standardized for effort and sighting conditions. Visual appraisals of data were made using a Geographical Information System. In contrast to historical perceptions, offshore areas such as the northern part of the Grand Banks (48–49°N and 49–51°W) appear to be extremely important to wintering harp seals. Southeastern shifts in distribution appear to have occurred since the early 1990s, particularly between the 1991–1993 and 1994–1995 periods. This southern shift in range agrees with the recent increase in extralimital occurrences of harp seals along the North American east coast. Concurrent changes in environmental conditions suggest that physical and biological factors may influence the distribution of this population. Accepted: 22 May 2000     

Spatial and temporal expression profiles suggest the involvement of gelatinase A and membrane type 1 matrix metalloproteinase in amphibian metamorphosis

The matrix metalloproteinases (MMPs) are a family of proteases capable of degrading various components of the extracellular matrix (ECM). Among them, the membrane type MMP–1 (MT1–MMP) has been shown to participate in the activation of MMP gelatinase A (GelA), suggesting that they may function together in development and pathogenesis. Here, we have investigated the spatiotemporal expression profiles of Xenopus laevis MT1–MMP and GelA genes during thyroid-hormone-dependent metamorphosis. We have focused our studies on two organs: (1) the intestine, which undergoes first the degeneration of the tadpole epithelium through apoptosis and then the development of adult epithelium and other tissues, and (2) the tail, which completely resorbs through programmed cell death. We show that both MT1–MMP and GelA are upregulated in the intestine and tail when both organs undergo metamorphosis. Within the organs, MT1–MMP and GelA are coexpressed in the connective tissues during both natural and thyroid-hormone-induced metamorphosis. In addition, MT1–MMP (but not GelA) is also expressed in the longitudinal muscle cells of the metamorphosing intestine. These results suggest that MT1–MMP and GelA function together in the ECM degradation or remodeling associated with metamorphosis and that MT1–MMP has additional GelA–independent roles in the development of adult longitudinal muscle in the intestine. This research was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH. T. Hasebe and H. Matsuda were supported in part by JSPS (NIH) fellowships.     

Palaeoenvironmental research on diatoms in early and middle Holocene deposits in central North Holland (The Netherlands)

In the geological research of the Holocene coastal deposits of The Netherlands, diatoms are used to reconstruct the sedimentary facies, palaeo-tide levels and salinity gradients during the deposition of the sediments. In this paper, the results of diatom research from 4 borings, taken from the early and middle Holocene deposits of central North Holland are presented. The oldest marine influenced sediments in the area are the deposits of the ‘Velsen layer’, a clay layer rich in organic matter and deposited about 8000–7000¹⁴C years before present (BP) at a depth of 20–12 m below present mean sea-level. This clay layer was formed in a shallow, permanently submerged environment with a limited tidal influence (lagoonal or pond-like conditions). The salinity changed from brackish/freshwater to marine/brackish. The younger sandy and clayey sediments, formed about 7000–4500 BP at a depth of 16–3 m below present mean sea-level, are classified as ‘tidal channel’ and ‘interchannel’ deposits. It is argued, on the base of both diatom and non-diatom criteria, that the lower and middle parts of the interchannel deposits in the central area of the palaeo-tidal basin of North Holland were formed in a subtidal environment. The upper part of the interchannel deposits and the deposits at the fringe of the North Holland tidal basin were formed in the intertidal zone or, at the fringe of the basin, even in the supratidal zone. The salinity in the North Holland tidal basin during the sedimentation of the tidal channel and interchannel deposits was marine/brackish to marine. This study indicates that diatoms, besides their palaeoecological applications, have chronostratigraphical significance (on a regional scale). The diatomsCymatosira belgica andActinoptychus splendens appear to be a useful (eco)stratigraphical marker in the Holocene coastal deposits of The Netherlands and Belgium.     

Spectroscopic studies on the interaction of bilirubin with liver cystatin

Studies on the role of endogenous metabolites such as bilirubin and their interactions with biomolecules have attracted considerable attention over the past several years. In this work, the interaction of bilirubin (BR) with purified goat liver cystatin (LC) was studied using fluorescence and ultraviolet (UV) spectroscopy. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR–cystatin complex formation. Stern–Volmer analysis of fluorescence quenching data showed the binding constant to be 9.27 × 10⁴ M⁻¹ and the number of binding sites to be close to unity. The conformation of the BR–cystatin complex was found to change upon varying the pH of the complex. The BR–cystatin complex was found to have reduced papain inhibitory activity. Photo-illumination of BR–cystatin complex causes perturbation in the micro-environment of goat liver cystatin as indicated by red-shift. This report summarizes our research efforts to reveal the mechanism of interaction of bilirubin with liver cystatin.     

Partitioning of biologically active radiation in plant canopies

 Plant germination, growth, maturation, and productivity are heavily influenced by the quality and quantity of the light in its environment. The light environment has traditionally been quantified in terms of radiant heat energy and available photosynthetic radiation (PAR), but detailed spectral irradiance or photon flux distributions have rarely been studied. This information is needed to translate the research that plant photobiologists and photochemists have been conducting with regard to understanding the light controls on plant physiology in the field environment of plant canopies. More interest has recently been generated as the potential impacts of global climate changes on intensively managed and natural terrestrial ecosystems are identified and evaluated. Linkages between the identified impacts of various wavelengths of light on plant physiology and the light environment of the plant canopy are identified, with detailed discussion concerning the impacts of plant canopy structure on the plant light response. Solar radiation in the ultraviolet-B (280–320 nm), ultraviolet-A and blue (350–500 nm), PAR (400–700 nm), blue (400–500 nm), green (500–600 nm) red (600–700 nm), far red (700–800 nm) and near infrared (800–1100 nm) is followed from the top of the plant canopy to the photoreceptor at the cellular level within the plant phytoelement.     

Changes in glutathione-related enzymes in tumor-bearing mice after cisplatin treatment

The effect of cisplatin on five glutathione-related enzymes was studied in liver, kidney, and Dalton lymphoma cells of tumor-bearing mice. In liver, the activities of glutathione S-transferase, glutathione peroxidase, catalase, and superoxide dismutase decreased approximately 30–40%, 60–67%, 35–50% and 70–80% respectively, while glutathione reductase increased about 36–45% after cisplatin treatment. In kidney, catalase activity decreased by 47–82% at all time points (24–96 h) of cisplatin treatment, while glutathione S-transferase activity decreased significantly (~24%) mainly at 72 h of treatment. An increase in glutathione reductase (~1.5–2.5 times), glutathione peroxidase (significant at 24 h, 47%), and superoxide dismutase (~15–60%) was noted in kidney after the treatment. In Dalton lymphoma cells, the activities of glutathione S-transferase, glutathione peroxidase, and catalase decreased very distinctly (~2–5, 2–5 and 5–11 times, respectively) at all time points, but glutathione reductase decreased significantly only at 72 h of cisplatin treatment. Interestingly, the superoxide dismutase activity in Dalton lymphoma cells increased initially at 24–48 h and then decreased (~60%) during later periods (72–96 h) of treatment. Cisplatin treatment caused a decrease in glutathione level in Dalton lymphoma cells (~14–20%) and kidney (~18–28%) but no change in liver. In view of the results, a definite correlation with the changes in glutathione concentrations and enzymatic activities in a tissue could not be firmly derived. It is suggested that the changes in various glutathione-related enzymes and glutathione levels in the tissues of the host during cisplatin-mediated chemotherapy could affect cellular antioxidant defense potential, which may play an important contributory role in cisplatin-mediated toxicity, particularly nephrotoxicity, and anticancer activity in the host. This revised version was published online in July 2006 with corrections to the Cover Date.     

Immunogenicity of synthetic fragments corresponding to variable and conservative sites of H3N2 influenza virus hemagglutinin heavy chain

Immunogenic properties of synthetic peptides corresponding to regions 122–133, 136–147, 154–164, and 314–328 of the heavy chain (HA1) of A/Aichi/2/68 virus hemagglutinin were studied. Peptides 122–133 and 136–147 together form a nearly complete antigenic determinant A, peptide 154–164 is a part of determinant B, and peptide 314–328 corresponds to the C-terminal HA1 fragment. In a model influenza A/Aichi/2/68 infection in CBA mice, a protective effect of conjugates of BSA with peptides 136–147 and 314–328 was shown. Immunization of animals with conjugates BSA-(136–147) and BSA-(314–328) in combination with interferon inducers (larifan and ridostin) and a plant immunomodulator (immunomax) intensified the protection of mice against the influenza infection.     

Ammonification in soil aggregates: Effect of some physical,physico-chemical and chemical properties

Aggregate diameter affected significantly the intensity of ammonification in chernozemic rendzina but not in lessivē soil. In the latter the process was influenced significantly by the number of microorganisms able to grow on asparagine agar. A high correlation, though not significant at the level of 0.05, was found between the ammonification intensity and the content of pores of radius: 3–1.5, 7.5–5.0, 0.5–0.25 and 0.01–0.005 μm in chernozemic rendzina and those measuring 1.5–0.5, 0.025–0.01, 0.01–0.005 and >7.5 μm in lessivē soil aggregates as well as the percentage of soil particles of 100–50 μm in chernozemic rendzina aggregates and the internal surface area and organic C in aggregates of lessivē soil.     

The biology of the spiny icefish <Emphasis Type="Italic">Chaenodraco wilsoni</Emphasis> Regan, 1914

The most abundant ice fish species observed in catches off the northern tip of the Antarctic Peninsula in the last 25–30 years has been the spiny ice fish Chaenodraco wilsoni Regan 1914. C. wilsoni has been exploited on a commercial scale from the late 1970s to the end of the 1980s off Joinville–D’Urville Islands (CCAMLR Statistical Subarea 48.1) and in the Cosmonauts and Cooperation Seas and Prydz Bay in the Indian Ocean sector (CCAMLR Statistical Division 58.4.2). This paper presents new information on biological features and life history characteristics of C. wilsoni, based on research survey collections along the northern Antarctic Peninsula in 2006 and 2007 and samples taken in the commercial fishery in 1987. Length frequency compositions from the research surveys demonstrated that fish 21–34 cm long predominated in the catches. Sexual maturity is attained at 24–25 cm. Absolute fecundity and relative fecundity is low (1,000–2,500 eggs; 6–12 eggs). Oocyte diameter varied from 4.0 to 4.9 mm very close to spawning. Spawning at the tip of the Antarctic Peninsula is likely to occur in October–November. Remotely operated vehicle deployments in the northern Weddell Sea demonstrated that C. wilsoni exhibit parental nest guarding where males protect the eggs. The incubation period is likely to be 8 months long. Fish feed primarily on Antarctic krill (Euphausia superba) in the Antarctic Peninsula region and in the Cosmonauts and Cooperation Seas while fish take ice krill (Euphausia crystallorophias), Pleuragramma antarcticum and myctophids to some extent in other areas. Age determination still awaits validation. Preliminary ageing attempts suggested a maximum age of about 8–10 years.     

Comparison of the Predicted Structures of Loops in the ras–SOS Protein Bound to a Single ras-p21 Protein with the Crystallographically Determined Structures in SOS Bound to Two ras-p21 Proteins

We have previously computed the structures of three loops, residues 591–596, 654–675 and 742–751, in the ras-p21 protein-binding domain (residues 568–1044) of the guanine nucleotide-exchange-promoting SOS protein that were crystallographically undefined when one molecule of ras-p21 (unbound to nucleotide) binds to SOS. Based on our computational results, we synthesized three peptides corresponding to sequences of each of these three loops and found that all three peptides strongly inhibit ras-p21 signaling. More recently, a new crystal structure of SOS has been determined in which this protein binds to two molecules of ras-p21, one unbound to GTP and one bound to GTP. In this structure, the 654–675 loop and residues 742–743 and 750–751 are now crystallographically defined. We have superimposed our energy-minimized structure of the ras-binding domain of SOS bound to one molecule of ras-p21 on the X-ray structure for SOS bound to two molecules of ras-p21. We find that, while the two structures are superimposable, there are large deviations of the residues 673 and 676 and 741 and 752, flanking the two loop segments. This suggests that the binding of the extra ras-p21 molecule, which is far from each of the three loops, induces conformational changes in these domains and further supports their role in signal transduction. In spite of these differences, we have superimposed our computed structures for the loop residues on those from the more recent X-ray structure. Our structure for the 654–675 segment is an anti-parallel beta-sheet with a reverse turn at residues 663–665; in the X-ray structure residues 655–662 adopt an alpha-helical conformation; on the other hand, our computed structure for residues 663–675 superimpose on the X-ray structure for these residues. We further find that our computed structures for residues 742–743 and 750–751 are superimposable on the X-ray structure for these residues.