1,757 research outputs found
Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells
Glycosylation is a highly complex process to produce a diverse repertoire of
cellular glycans that are attached to proteins and lipids. Glycans are involved
in fundamental biological processes, including protein folding and clearance,
cell proliferation and apoptosis, development, immune responses, and
pathogenesis. One of the major types of glycans, N-linked glycans, is formed by
sequential attachments of monosaccharides to proteins by a limited number of
enzymes. Many of these enzymes can accept multiple N-linked glycans as
substrates, thereby generating a large number of glycan intermediates and their
intermingled pathways. Motivated by the quantitative methods developed in
complex network research, we investigated the large-scale organization of such
N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation
pathways are extremely modular, and are composed of cohesive topological
modules that directly branch from a common upstream pathway of glycan
synthesis. This unique structural property allows the glycan production between
modules to be controlled by the upstream region. Although the enzymes act on
multiple glycan substrates, indicating cross-talk between modules, the impact
of the cross-talk on the module-specific enhancement of glycan synthesis may be
confined within a moderate range by transcription-level control. The findings
of the present study provide experimentally-testable predictions for
glycosylation processes, and may be applicable to therapeutic glycoprotein
engineering
High Cleavage Efficiency of a 2A Peptide Derived from Porcine Teschovirus-1 in Human Cell Lines, Zebrafish and Mice
When expression of more than one gene is required in cells, bicistronic or
multicistronic expression vectors have been used. Among various strategies
employed to construct bicistronic or multicistronic vectors, an internal
ribosomal entry site (IRES) has been widely used. Due to the large size and
difference in expression levels between genes before and after IRES, however, a
new strategy was required to replace IRES. A self-cleaving 2A peptide could be a
good candidate to replace IRES because of its small size and high cleavage
efficiency between genes upstream and downstream of the 2A peptide. Despite the
advantages of the 2A peptides, its use is not widespread because (i) there are
no publicly available cloning vectors harboring a 2A peptide gene and (ii)
comprehensive comparison of cleavage efficiency among various 2A peptides
reported to date has not been performed in different contexts. Here, we
generated four expression plasmids each harboring different 2A peptides derived
from the foot-and-mouth disease virus, equine rhinitis A virus, Thosea
asigna virus and porcine teschovirus-1, respectively, and evaluated
their cleavage efficiency in three commonly used human cell lines, zebrafish
embryos and adult mice. Western blotting and confocal microscopic analyses
revealed that among the four 2As, the one derived from porcine teschovirus-1
(P2A) has the highest cleavage efficiency in all the contexts examined. We
anticipate that the 2A-harboring cloning vectors we generated and the highest
efficiency of the P2A peptide we demonstrated would help biomedical researchers
easily adopt the 2A technology when bicistronic or multicistronic expression is
required
Prompt atmospheric neutrino fluxes: perturbative QCD models and nuclear effects
We evaluate the prompt atmospheric neutrino flux at high energies using three
different frameworks for calculating the heavy quark production cross section
in QCD: NLO perturbative QCD, factorization including low-
resummation, and the dipole model including parton saturation. We use QCD
parameters, the value for the charm quark mass and the range for the
factorization and renormalization scales that provide the best description of
the total charm cross section measured at fixed target experiments, at RHIC and
at LHC. Using these parameters we calculate differential cross sections for
charm and bottom production and compare with the latest data on forward charm
meson production from LHCb at TeV and at TeV, finding good agreement
with the data. In addition, we investigate the role of nuclear shadowing by
including nuclear parton distribution functions (PDF) for the target air
nucleus using two different nuclear PDF schemes. Depending on the scheme used,
we find the reduction of the flux due to nuclear effects varies from to
at the highest energies. Finally, we compare our results with the
IceCube limit on the prompt neutrino flux, which is already providing valuable
information about some of the QCD models.Comment: 61 pages, 25 figures, 11 table
Scalable Purification and Characterization of the Anticancer Lunasin Peptide from Soybean
Lunasin is a peptide derived from the soybean 2S albumin seed protein that has both anticancer and anti-inflammatory activities. Large-scale animal studies and human clinical trials to determine the efficacy of lunasin in vivo have been hampered by the cost of synthetic lunasin and the lack of a method for obtaining gram quantities of highly purified lunasin from plant sources. The goal of this study was to develop a large-scale method to generate highly purified lunasin from defatted soy flour. A scalable method was developed that utilizes the sequential application of anion-exchange chromatography, ultrafiltration, and reversed-phase chromatography. This method generates lunasin preparations of >99% purity with a yield of 442 mg/kg defatted soy flour. Mass spectrometry of the purified lunasin revealed that the peptide is 44 amino acids in length and represents the original published sequence of lunasin with an additional C-terminal asparagine residue. Histone-binding assays demonstrated that the biological activity of the purified lunasin was similar to that of synthetic lunasin. This study provides a robust method for purifying commercial-scale quantities of biologically-active lunasin and clearly identifies the predominant form of lunasin in soy flour. This method will greatly facilitate the development of lunasin as a potential nutraceutical or therapeutic anticancer agent
Scaling Laws in Human Language
Zipf's law on word frequency is observed in English, French, Spanish,
Italian, and so on, yet it does not hold for Chinese, Japanese or Korean
characters. A model for writing process is proposed to explain the above
difference, which takes into account the effects of finite vocabulary size.
Experiments, simulations and analytical solution agree well with each other.
The results show that the frequency distribution follows a power law with
exponent being equal to 1, at which the corresponding Zipf's exponent diverges.
Actually, the distribution obeys exponential form in the Zipf's plot. Deviating
from the Heaps' law, the number of distinct words grows with the text length in
three stages: It grows linearly in the beginning, then turns to a logarithmical
form, and eventually saturates. This work refines previous understanding about
Zipf's law and Heaps' law in language systems.Comment: 6 pages, 4 figure
Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ^1H molecular diffusion NMR and ^(19)F spin diffusion NMR
R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ^1H molecular diffusion nuclear magnetic resonance (NMR) and ^(19)F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ^(19)F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications
Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype
Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions
Emergence of scale-free leadership structure in social recommender systems
The study of the organization of social networks is important for
understanding of opinion formation, rumor spreading, and the emergence of
trends and fashion. This paper reports empirical analysis of networks extracted
from four leading sites with social functionality (Delicious, Flickr, Twitter
and YouTube) and shows that they all display a scale-free leadership structure.
To reproduce this feature, we propose an adaptive network model driven by
social recommending. Artificial agent-based simulations of this model highlight
a "good get richer" mechanism where users with broad interests and good
judgments are likely to become popular leaders for the others. Simulations also
indicate that the studied social recommendation mechanism can gradually improve
the user experience by adapting to tastes of its users. Finally we outline
implications for real online resource-sharing systems
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