Modeling for evolving biological networks with scale-free connectivity, hierarchical modularity, and disassortativity

We propose a growing network model that consists of two tunable mechanisms: growth by merging modules which are represented as complete graphs and a fitness-driven preferential attachment. Our model exhibits the three prominent statistical properties are widely shared in real biological networks, for example gene regulatory, protein-protein interaction, and metabolic networks. They retain three power law relationships, such as the power laws of degree distribution, clustering spectrum, and degree-degree correlation corresponding to scale-free connectivity, hierarchical modularity, and disassortativity, respectively. After making comparisons of these properties between model networks and biological networks, we confirmed that our model has inference potential for evolutionary processes of biological networks.     

Invertebrate dispersal and habitat heterogeneity: Expression of biological traits in a seagrass landscape

Seagrass meadows harbour diverse faunal assemblages, but the relative importance of landscapes attributes, settlement processes and biological traits of individual species for recruitment patterns is poorly understood. To quantify the influence of habitat heterogeneity on larval, juvenile and adult post-larval dispersal, invertebrates (> 125 µm) were collected in benthic settlement traps at five occasions (June-August) in three habitats; continuous seagrass, seagrass patches and bare sand. The study was carried out by SCUBA diving in a subtidal (2.5 m depth) seagrass landscape dominated by Zostera marina L. in the Baltic Sea. Traps collected totally > 30 taxa, with non-significant effects of habitat on species richness and total abundance. Total number of invertebrates exhibited strong temporal variability, probably driven by wind-induced bedload and water column transport. Surprisingly, traps located in small (< 12 m²) patches contained on average almost twice as many individuals as traps located in the continuous vegetation. Dominating taxa such as nematodes, copepods, and oligochaetes were found in similar densities across the landscape. In contrast, location within the landscape had strong effects on bivalve settlement and redistribution patterns, resulting in significantly lower densities in continuous vegetation compared to patches and bare sand. A biological trait analysis indicated that semi-mobile taxa with annual protracted direct development, and short-distance dispersal are probably of higher importance for the community assembly process in this environment than long-distance larval dispersal. Results suggest that seagrass landscapes are highly dynamic environments, characterized by time and species-specific effects of landscape attributes on animal dispersal and recruitment. A conceptual model illustrating interactions between settling larvae and landscape heterogeneity is presented.     

Design,synthesis and biological activity of a novel ethylenediamine derivatives as H1 receptor antagonists

In this study, a series of novel ethylenediamine compounds were obtained by structural modification of the lead compounds with thonzylamine, and using the principle of modifying by bioisostere formation and modification with alkyl groups. In vitro assay, the biological activities showed that the target compounds have good properties in inhibiting mast cell degranulation and releasing histamine and β-aminohexidase, such as the compounds 5c, 5g, 5k, 5l and 5o, especially of compound 5k to mast cell degranulation is IC₅₀ = 0.0106 ± 0.001 μmol?L^?1, histamine release was IC₅₀ = 0.0192 ± 0.005 μmol?L^?1 and β-hexosaminidase release was IC₅₀ = 0.0455 ± 0.002 μmol?L^?1 in vitro. At the same time, in vivo biological activities assay results showed that have a good Histamie induce bronchospasm effect with relatively long duration and good protective effect in vivo, among which the protective effect of compound 5k was 79.74 ± 0.30%, compounds 5c, 5g, 5k, 5l and 5o could inhibit the capillary permeability of increasing which were caused by histamine.     

The biological standard of living (and its convergence) in Colombia, 1870–2003: A tropical success story

During the 20th century, the evolution of the biological standard of living in Colombia was a tropical success story from the point of view of the secular increase in height as well as the reduction of inequality. During the period 1905-1985 the average height of females and males increased by nearly 9 cm on the basis of 9 million records examined from National Identification Cards. We also study the evolution of height of Colombians on the basis of passport records. The elite group of passport holders was much taller than average, and remained stable for the birth cohorts of 1870-1919. In the early 20th century the height of passport recipients was 168.7 cm (men) and 158 cm (women) compared with 162 cm and 150 cm for heights in the national ID cards. The results also show that Colombians experienced significant regional and intrapersonal convergence in height.     

Synthesis,biological evaluation and molecular modeling of a novel series of fused 1,2,3-triazoles as potential anti-coronavirus agents

Synthesis and biological evaluation of a novel library of fused 1,2,3-triazole derivatives are described. The in-house developed multicomponent reaction based on commercially available starting materials was applied and broad biological screening against various viruses was performed, showing promising antiviral properties for compounds 14d, 14n, 14q, 18f and 18i against human coronavirus 229E. Further in silico studies identified the key molecular interactions between those compounds and the 3-chymotrypsin-like protease, which is essential to the intracellular replication of the virus, supporting the hypothesis that the protease is the target molecule of the potential antiviral derivatives.     

Neuronal targeting, internalization, and biological activity of a recombinant atoxic derivative of botulinum neurotoxin A

Non-toxic derivatives of botulinum neurotoxin A (BoNT/A) have potential use as neuron-targeting delivery vehicles, and as reagents to study intracellular trafficking. We have designed and expressed an atoxic derivative of BoNT/A (BoNT/A ad) as a full-length 150 kDa molecule consisting of a 50 kDa light chain (LC) and a 100 kDa heavy chain (HC) joined by a disulfide bond and rendered atoxic through the introduction of metalloprotease-inactivating point mutations in the light chain. Studies in neuronal cultures demonstrated that BoNT/A ad cannot cleave synaptosomal-associated protein 25 (SNAP25), the substrate of wt BoNT/A, and that it effectively competes with wt BoNT/A for binding to endogenous neuronal receptors. In vitro and in vivo studies indicate accumulation of BoNT/A ad at the neuromuscular junction of the mouse diaphragm. Immunoprecipitation studies indicate that the LC of BoNT/A ad forms a complex with SNAP25 present in the neuronal cytosolic fraction, demonstrating that the atoxic LC retains the SNAP25 binding capability of the wt toxin. Toxicity of BoNT/A ad was found to be reduced approximately 100,000-fold relative to wt BoNT/A.     

TCDD as a biological response modifier for Mitomycin C: oxygen tension affects enzyme activation, reactive oxygen species and cell death

TCDD was assessed as a biological response modifier for increasing MMC cytotoxicity through aryl hydrocarbon receptor (AhR) activation and increasing levels of bioreductive enzymes. Human MCF-7 cells were exposed to TCDD, MMC and combinations thereof under aerobic or hypoxic conditions. Cytotoxicity, enzyme activities (NQO1, XO, XDH, CYPR, CYP1A, GST and UGT) and intracellular reactive oxygen species (ROS) were subsequently measured. Under aerobic conditions, TCDD alone had no significant toxicity but combinations of TCDD and MMC significantly increased cell death. LD50 values were: MMC alone, 0.89 +/- 0.04 microM; TCDD co-treatment, 0.26 +/- 0.007 microM (P = 0.008 vs. MMC alone) and TCDD pre-treatment, 0.04 +/- 0.01 microM (P = 0.003 vs. MMC alone). Under hypoxia, TCDD itself caused significant cell death, likely due to increased ROS, but no combinations of MMC/TCDD altered the LD50 of MMC. Significant changes in enzyme activities were caused by TCDD under aerobic but not hypoxic conditions while MMC decreased the activity of its activating enzymes regardless of oxygen tension. Greater toxicity of MMC/TCDD combinations in aerobic culture, were most likely mediated by increased levels of bioreductive enzymes caused through AhR activation. Data presented herein also demonstrate that low oxygen tension decreases AhR activation and signaling and increases the inherent toxicity of TCDD.     

Design,synthesis, nuclear localization,and biological activity of a fluorescent duocarmycin analog,HxTfA

HxTfA 4 is a fluorescent analog of a potent cytotoxic and antimalarial agent, TfA 3, which is currently being investigated for the development of an antimalarial vaccine, PlasProtect®. HxTfA contains a p-anisylbenzimidazole or Hx moiety, which is endowed with a blue emission upon excitation at 318?nm; thus enabling it to be used as a surrogate for probing the cellular fate of TfA using confocal microscopy, and addressing the question of nuclear localization. HxTfA exhibits similar selectivity to TfA for A-tract sequences of DNA, alkylating adenine-N3, albeit at 10-fold higher concentrations. It also possesses in vitro cytotoxicity against A549 human lung carcinoma cells and Plasmodium falciparum. Confocal microscopy studies showed for the first time that HxTfA, and by inference TfA, entered A549 cells and localized in the nucleus to exert its biological activity. At biologically relevant concentrations, HxTfA elicits DNA damage response as evidenced by a marked increase in the levels of γH2AX observed by confocal microscopy and immunoblotting studies, and ultimately induces apoptosis.     

Specific oxygen, ammonia, and nitrate uptake rates of a biological nutrient removal process treating elevated salinity wastewater

Anaerobic/anoxic/aerobic systems inoculated without and with NaCl acclimated cultures, i.e., Models A and B, respectively, were fed with a synthetic wastewater at various salinity levels. After achieving a steady state, the systems were shocked with 70 g/l NaCl for four consecutive days before returning to pre-shock conditions. At the steady-state, the specific oxygen uptake rates (SOURs) increased with an increase of sodium chloride concentration (from 5.40 to 9.72 mg O₂/g mixed liquor suspended solids (MLSS)-h at 0–30 g/l NaCl for Model A and from 6.84 to 17.64 mg O₂/g MLSS-h at 5–30 g/l NaCl for Model B). In contrast, the specific ammonia uptake rate (SAUR) and specific nitrate uptake rate (SNUR) decreased with increasing chloride concentration (from 4.76 to 2.14 mg NH₃–N/g MLSS-h and 2.50 to 1.22 NO3–N/g MLSS-h, for Model A, and from 3.84 to 2.71 mg NH₃–N/g MLSS-hr and 2.54 to 1.82 mg NO₃–N/g MLSS-hr, for Model B). During the shocked period, the SOUR in most scenarios increased whereas the SAUR and SNUR tended to decrease. The impact of the chloride shock on nitrifiers was more obvious than on denitrifiers; however, after a certain recovery period, the activities of both nitrifiers and denitrifiers in terms of SAUR and SNUR were approximately the same as those prior to shock.     

Physical, chemical and microscopic characterization of a new starch from chayote (Sechium edule) tuber and its comparison with potato and maize starches

In this work, the chayote tuber starch (CHS) was isolated and its chemical composition and its physical and microscopic characteristics were determined, and compared with potato (PS) and maize (MS) starches. The starch content in chayote tubers (728 g kg⁻¹ dry weight) was similar to potato tubers (700 g kg⁻¹ dry weight), with a high level of purity (>98%), while its phosphorous content was higher (0.15%) than PS (0.08%) and MS (0.01%). Starch granules were oval, irregular, truncated and rounded with sizes between 7 and 50 μm with smooth surfaces. CHS dispersions (1% and 4%, w/w) showed higher viscosity (75 and 1715 mPa s), than PS (350% and 50% lower) and MS (715% and 600% lower). The gelatinization temperature (65 to 74 °C) was similar in CHS and PS. The pasting properties (RVA) of the starches suggest that CHS showed better characteristics than the commercial potato and maize starches. Therefore, CHS could be used as a thickening agent and a substitute to PS in food dispersions where a high viscosity is needed.     

Release and establishment of a biological control agent, Psyllaephagus pilosus for eucalyptus psyllid (Ctenarytaina eucalypti) in Ireland

An Australian parasitoid wasp, Psyllaephagus pilosus, was collected from a previous release site in France and introduced into a commercial eucalyptus foliage plantation in Co. Kerry in the south west of Ireland to control the eucalyptus (blue gum) psyllid Ctenarytaina eucalypti. The first parasitised psyllid nymphs were observed 26 days after the release was made in late May 1998, and 49 days elapsed before a new generation of adult parasitoids was seen. Visually assessed indices of psyllid parasitism and adult wasp incidence were used to quantify the pattern of adult dispersion and establishment. A second generation of adult wasps emerged in late August, initiating a rapid spread of parasitism throughout the release site during September that culminated in a peak rate of almost 100% parasitism by late October. Subsequently by the end of 1998, an apparently random process of dispersion and successful natural colonisation occurred at eight out of ten monitored plantations at distances up to 70 km from the release point. The first colonisers of the other two sites arrived very late in 1998, and consequently failed to establish viable populations by the following summer. Probably this failure was because the small numbers of colonisers had arrived too late in the growing season to effect population establishment before the onset of winter. Assisted introductions were, therefore, made at these sites in June and August 1999, respectively. Once fully established, the parasitoid had no difficulty in surviving winter conditions at all monitored sites and demonstrated excellent potential as a biological control agent.     

Formulation of a coupled mechanism between solute diffusion,phosphatase-kinase reactions and membrane potentials for the primary active transport of phosphorylated substrates through biological membranes

Coupled interrelations occurring between a phosphatase/kinase reaction sequence acting in unstirred layers and on both sides of a charged biomembrane pore structure are presented as a plausible kinetic model for the primary active transport of phosphorylated molecules. Simulations conducted at the cell level and with credible numerical values demonstrate that the enzymes positions strongly regulate the membrane permeability for the transported substrate. Depending on both the enzymes positions (more or less far from the membrane) and the membrane charges, the membrane may appear either impervious, either permeable or able to actively transport a phosphorylated substrate. Globally all happens as if, in function of the enzymes positions, a permanent pore may be regulated, changing from a more closed to a more open conformation.     

Structure and biological activity of maculansin A, a phytotoxin from the phytopathogenic fungus Leptosphaeria maculans

During a search for elicitors and phytotoxins produced by virulent isolates of the phytopathogenic fungus Leptosphaeria maculans (Desm.) Ces. et de Not. [asexual stage Phomalingam (Tode ex Fr.) Desm.], the selective phytotoxin maculansin A was isolated and its structure determined by analysis of spectroscopic data and chemical degradation. Maculansin A, a unique derivative of mannitol containing the unusual chromophore 2-isocyano-3-methyl-2-butenoyl, was isolated from potato dextrose cultures of L. maculans virulent on canola (Brassica napus L. cv. Westar). Surprisingly, maculansin A was more toxic to resistant plants (B. juncea L. cv. Cutlass, brown mustard) than to susceptible plants (canola). Maculansin A, however, did not elicit the production of phytoalexins either in resistant or susceptible plants. In addition, other maculansin type structures and the metabolite 2,4-dihydroxy-3,6-dimethylbenzaldehyde were isolated and the latter was found to be a strong inhibitor of root growth of both brown mustard and canola. Considering that L. maculans seems to be expanding its host range to infect brown mustard as well, maculansins could assist in chemotaxonomic studies to group the diverse isolates.     

Identification of the up-regulation of TP-alpha, collagen alpha-1(VI) chain, and S100A9 in esophageal squamous cell carcinoma by a proteomic method

Esophageal squamous cell carcinoma (ESCC) is one of the most common primary malignant tumor of digestive tract. However, the early diagnosis and molecular mechanisms that underlie tumor formation and progression have been progressed less. To identify new biomarkers for ESCC, we performed a comparative proteomic research. Isobaric tags for relative and absolute quantitation-based proteomic method was used to screen biomarkers between ESCC and normal. 802 non-redundant proteins were identified, 39 of which were differentially expressed with 1.5-fold difference (29 up-regulated and 10 down-regulated). Through Swiss-Prot and GO database, the location and function of differential proteins were analyzed, which are related to the biological processes of binding, cell structure, signal transduction, cell adhesion, etc. Among the differentially expressed proteins, TP-alpha, collagen alpha-1(VI) chain and S100A9 were verified to be upregulated in 77.19%, 75.44% and 59.65% of ESCC by immunohistochemistry and western-blot. Diagnostic value of these three proteins was validated. These results provide new insights into ESCC biology and potential diagnostic and therapeutic biomarkers, which suggest that TP-alpha, collagen alpha-1(VI) chain and S100A9 are potential biomarkers of ESCC, and may play an important role in tumorigenesis and development of ESCC.     

The ApoCorrect assay: a novel, rapid method to determine the biological functionality of radiolabeled and fluorescent Annexin A5

N-[4-(3)H]Benzoylglycylglycylglycine ([(3)H]BzG(3)) was tested as a probe for detecting hydroxyl radicals (*OH). Aerated solutions of l-ascorbate generated *OH, which oxidized [(3)H]BzG(3), yielding hydrophilic (probably hydroxylated) derivatives plus tritiated water. The (3)H(2)O was separated from organic products and remaining [(3)H]BzG(3) on Dowex-1. (3)H(2)O production was much greater with *OH than with other reactive oxygen species (ROS) (e.g., H(2)O(2), superoxide). The slight (3)H(2)O production in the presence of H(2)O(2) or superoxide was blocked by *OH scavengers (e.g., glycerol, mannitol, butan-1-ol) that do not scavenge H(2)O(2) or superoxide. This indicates that (3)H(2)O production was caused by *OH and that other ROS only generated any (3)H(2)O by forming traces of *OH. Doses of *OH that caused detectable nonenzymic polysaccharide scission also caused (3)H(2)O production, indicating that [(3)H]BzG(3) is a sensitive *OH probe in studies of polymer scission. The ability of scavengers and chelators to protect against ascorbate-mediated polysaccharide scission paralleled their ability to inhibit concurrent (3)H(2)O production, indicating that both processes were due to *OH. Thus, [(3)H]BzG(3) is a simple, specific, sensitive, and robust probe for detecting *OH production in vitro. It may have applications for in vivo detection of extracellular *OH in arthritic joints and of apoplastic *OH in plant cell walls.     

Host specificity ofPterolonche inspersa [Lep.: Pterolonchidae] and its potential as a biological control agent forCentaurea diffusa,diffuse knapweed,andC. Maculosa,spotted knapweed

In 1981 the United States Department of Agriculture (USDA) Biological Control of Weeds Laboratory (BCWL, Rome, Italy) started investigating the host specificity ofP. inspersa as a candidate for biological control ofC. diffusa andC. maculosa, and in 1985 the investigation was completed at the USDA Biological Control of Weeds Laboratory at Albany, California. Thirty five species of plants in the familyAsteraceae and 23 other species in 8 related families were tested. Larval survival beyond 1st instar occurred only onCentaurea spp. except for 1 larva found inCnicus benedictus L.P. inspersa is stenophagous onCentaurea, therefore, a good candidate for introduction into North America.      

Conceptual, methodological and computational issues concerning the compartmental modeling of a complex biological system: Postprandial inter-organ metabolism of dietary nitrogen in humans

A multi-compartmental model has been developed to describe dietary nitrogen (N) postprandial distribution and metabolism in humans. This paper details the entire process of model development, including the successive steps of its construction, parameter estimation and validation. The model was built using experimental data on dietary N kinetics in certain accessible pools of the intestine, blood and urine in healthy adults fed a [15N]-labeled protein meal. A 13-compartment, 21-parameter model was selected from candidate models of increasing order as being the minimum structure able to properly fit experimental data for all sampled compartments. Problems of theoretical identifiability and numerical identification of the model both constituted mathematical challenges that were difficult to solve because of the large number of unknown parameters and the few experimental data available. For this reason, new robust and reliable methods were applied, which enabled (i) a check that all model parameters could theoretically uniquely be determined and (ii) an estimation of their numerical values with satisfactory precision from the experimental data. Finally, model validation was completed by first verifying its a posteriori identifiability and then carrying out external validation.     

Physical and biological processes influencing zonation patterns of a subtidal population of the marine snail, Astraea (Lithopoma) undosa Wood 1828

The population density and size distribution of the marine gastropod, Astraea (Lithopoma) undosa Wood 1828, at Bird Rock, Santa Catalina Island, CA, reveal an inverse relationship between population density and mean individual size, over a depth gradient. This trend may be correlated with physical and biological differences between habitats for parameters such as water motion, competitive interactions, and predation.

The potential effect of hydrodynamic forces on the zonation patterns of Astraea undosa was tested in laboratory and field experiments. Based on theoretical predictions of the relationship between shear force and water velocity on different-sized snails, large snails are subjected to greater shear forces, as a result of water motion, than medium or small snails. Results of dislodgment experiments conducted in the laboratory indicated that for a given force per unit area, all snails dislodged at nearly the same frequency, with 50% of snails predicted to dislodge at about 4 m/s, and 100% of snails predicted to dislodge at about 8 m/s velocity. These results suggest that hydrodynamic forces may be an important factor in the shallowest subtidal zones.

A factorial-designed caging experiment was used to test the effects of snail population density on growth rates of snails of three different size classes. For small and medium size classes, results indicated an inverse relationship between population density and growth rates, which was especially pronounced for smaller snails. These data, in conjunction with long-term patterns of population density and size distribution in the field, suggest that intraspecific competition also plays a role in determining size-specific zonation patterns.

Tethering experiments, used to estimate predation rates in different algal-cover zones, suggest that there are no differences in survival rates among different snail size classes; however, survival rates differ among zones and may contribute further to the observed zonation patterns. Overall, data indicate that a combination of physical and biological processes controls the population density and size-distribution of Astraea undosa over a depth gradient at Santa Catalina Island, California.     

2-(2-Methylfuran-3-carboxamido)-3-phenylpropanoic acid,a potential CYP26A1 inhibitor to enhance all-trans retinoic acid-induced leukemia cell differentiation based on virtual screening and biological evaluation

To develop new CYP26A1 inhibitors, a three-cycle virtual screening was carried out based on the constructed homology model of human CYP26A1 using Dock, Fred, Gold and AutoDock. Twenty-two compounds exhibited high scores and reasonable binding modes in molecular docking were purchased from Specs Company. Eighteen compounds were tested their abilities to enhance ATRA-induced differentiation in human acute promyelocytic leukemia NB4 cells. Eight of them enhanced the ability of ATRA to induce differentiation at concentrations of 0.5 and 1 μM. Among these compounds, 2-(2-methylfuran-3-carboxamido)-3-phenylpropanoic acid (S8) is of most effective in blocking ATRA breaking down in NB4 cells based on the LC–MS/MS assay.