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1.
Phys Rev E ; 109(1-2): 015206, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38366478

ABSTRACT

Understanding magnetic field growth in astrophysical objects is a persistent challenge. In stars and galaxies, turbulent flows with net kinetic helicity are believed to be responsible for driving large-scale magnetic fields. However, numerical simulations have demonstrated that such helical dynamos in closed volumes saturate at lower magnetic field strengths when increasing the magnetic Reynolds number Rm. This would imply that helical large-scale dynamos cannot be efficient in astrophysical bodies without the help of helicity outflows such as stellar winds. But do these implications actually apply for very large Rm? Here we tackle the long-standing question of how much helical large-scale dynamo growth occurs independent of Rm in a closed volume. We analyze data from numerical simulations with a new method that tracks resistive versus nonresistive drivers of helical field growth. We identify a presaturation regime when the large-scale field grows at a rate independent of Rm, but to an Rm-dependent magnitude. The latter Rm dependence is due to a dominant resistive contribution, but whose fractional contribution to the large-scale magnetic energy decreases with increasing Rm. We argue that the resistive contribution would become negligible at large Rm and an Rm-independent dynamical contribution would dominate if the current helicity spectrum in the inertial range is steeper than k^{0}. As such helicity spectra are plausible, this renews optimism for the relevance of closed dynamos. Our work pinpoints how modest Rm simulations can cause misapprehension of the Rm→∞ behavior.

2.
FASEB J ; 26(9): 3811-21, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22649032

ABSTRACT

Nerve growth factor (NGF) is a dimeric molecule that modulates the survival, proliferation, and differentiation of nervous cells and is also known to act on cells of the immune system and endocrine system. NGFs extracted from mouse submaxillary gland and cobra venom have different immunological behaviors, yet the underlying mechanism remains unclear. Here we report the crystal structure of the NGF purified from Chinese cobra Naja naja atra (cNGF), which unexpectedly reveals a 2-tailed lipid molecule that is embedded between the two protomers of the NGF homodimer. In addition, crystallographic analysis indicated that the purified mouse NGF(mNGF) is free from lipid but can bind lysophosphatidylserine (lyso-PS) in the same pocket as cNGF. Bioassays indicated that the binding of lipid molecules to cNGF and mNGF are essential for their mast cell activation activity and abates their p75(NTR) binding capacity. Taken together, these results suggest a new mechanism for the regulation of the function of NGF.


Subject(s)
Lipids/chemistry , Nerve Growth Factors/chemistry , Nerve Growth Factors/pharmacology , Amino Acid Sequence , Animals , Crystallography, X-Ray , Elapidae , Histamine Release/drug effects , Humans , Mast Cells/drug effects , Models, Molecular , Molecular Sequence Data , Nerve Growth Factors/isolation & purification , Nerve Growth Factors/metabolism , Sequence Homology, Amino Acid , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Structure-Activity Relationship
3.
PLoS One ; 4(6): e6087, 2009 Jun 30.
Article in English | MEDLINE | ID: mdl-19564921

ABSTRACT

BACKGROUND: Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach. METHODOLOGY/PRINCIPAL FINDINGS: In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1) and one mouse self-antigen (TNF-alpha) as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system. CONCLUSIONS/SIGNIFICANCE: We developed an efficient and universal method for generating surrogate or therapeutic antibodies against "difficult antigens" to facilitate the development of therapeutic antibodies.


Subject(s)
Antibodies, Monoclonal/chemistry , HMGB1 Protein/immunology , Intramolecular Oxidoreductases/metabolism , Macrophage Migration-Inhibitory Factors/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Cell Line , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immune System , Lipopolysaccharides/metabolism , Mice , Mice, Inbred BALB C , Models, Statistical , Recombinant Proteins/chemistry
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