Generation of Monoclonal Antibodies against Highly Conserved Antigens

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 therapeuti

Effect of Aged Wuyi Rock Tea on Relieving Dextran Sulfate Sodium-Induced Colitis and Regulating the Gut Microbiota in Mice

This research was performed in order to investigate the alleviative effect of aged Wuyi rock tea on dextran sulfate sodium (DSS)-induced colitis in mice. Fifty C57BL/6JGpt female mice were randomly and equally divided into five groups: control, DSS, DSS + infusion of 20-year-old Wuyi rock tea (DSS + OT01), DSS + infusion of 10-year-old Wuyi rock tea (DSS + OT11) and DSS + infusion of fresh Wuyi rock tea (DSS + OT20). The physiological and histopathological conditions of mice after Wuyi rock tea interventions, and the changes of serum inflammatory factors and cecal microbiota were analyzed. The results showed that aged Wuyi rock tea could significantly alleviate the symptoms of body mass loss, diarrhea, bloody stool, and colon length shortening, reduce inflammatory cell infiltration, and significantly inhibit the secretion of pro-inflammatory cytokines. In addition, aged Wuyi rock tea could alleviate the disorder of the gut microbiota, significantly down-regulate the relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia, and up-regulate the relative abundance of Verrucomicrobia and Akkermansia. In summary, aged Wuyi rock tea can alleviate DSS-induced colitis in mice, and the tea produced in 2011 is more effective than that produced in 2001, which may be due to proper oxidation of catechins such as epigallocatechin gallate to produce thearubigins, with better anti-inflammatory and antioxidant properties. In addition, aged Wuyi rock tea is able to maintain intestinal homeostasis by regulating the relative abundance of Escherichia and Akkermansia in the intestine, which in turn alleviates the symptoms of DSS-induced colitis in mice such as body mass loss, diarrhea, bloody stool, colon length shortening, mucosal and crypt damage, inflammatory cell infiltration, and serum inflammatory factor overexpression

Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and perturbed respiratory metabolism. Mice lacking PPP1R3A are protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify previously unreported cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description of PPP1R3A as a central regulator in heart failure

SirT1 modulates the estrogen–insulin-like growth factor-1 signaling for postnatal development of mammary gland in mice

INTRODUCTION: Estrogen and insulin-like growth factor-1 (IGF-1) play important roles in mammary gland development and breast cancer. SirT1 is a highly conserved protein deacetylase that can regulate the insulin/IGF-1 signaling in lower organisms, as well as a growing number of transcription factors, including NF-κB, in mammalian cells. Whether SirT1 regulates the IGF-1 signaling for mammary gland development and function, however, is not clear. In the present study, this role of SirT1 was examined by studying SirT1-deficient mice. METHODS: SirT1-deficient (SirT1(ko/ko)) mice were generated by crossing a new strain of mice harboring a conditional targeted mutation in the SirT1 gene (SirT1(co/co)) with CMV-Cre transgenic mice. Whole mount and histology analyses, immunofluorescence staining, immunohistochemistry, and western blotting were used to characterize mammary gland development in virgin and pregnant mice. The effect of exogenous estrogen was also examined by subcutaneous implantation of a slow-releasing pellet in the subscapular region. RESULTS: Both male and female SirT1(ko/ko )mice can be fertile despite the growth retardation phenotype. Virgin SirT1(ko/ko )mice displayed impeded ductal morphogenesis, whereas pregnant SirT1(ko/ko )mice manifested lactation failure due to an underdeveloped lobuloalveolar network. Estrogen implantation was sufficient to rescue ductal morphogenesis. Exogenous estrogen reversed the increased basal level of IGF-1 binding protein-1 expression in SirT1(ko/ko )mammary tissues, but not that of IκBα expression, suggesting that increased levels of estrogen enhanced the production of local IGF-1 and rescued ductal morphogenesis. Additionally, TNFα treatment enhanced the level of the newly synthesized IκBα in SirT1(ko/ko )cells. SirT1 deficiency therefore affects the cellular response to multiple extrinsic signals. CONCLUSION: SirT1 modulates the IGF-1 signaling critical for both growth regulation and mammary gland development in mice. SirT1 deficiency deregulates the expression of IGF-1 binding protein-1 and attenuates the effect of IGF-1 signals, including estrogen-stimulated local IGF-1 signaling for the onset of ductal morphogenesis. These findings suggest that the enzymatic activity of SirT1 may influence both normal growth and malignant growth of mammary epithelial cells

Controllable preparation of iron nanostructure/carbon nanotube composite materials and their microwave absorption properties

International audienceIron nanoparticles, iron nanochains and composite materials of iron nanoparticles and carbon nanotubes were prepared using a simple reduction method. The complex permittivity and complex permeability in the frequency range of 1–18 GHz were measured, upon which the reflection loss was calculated. Iron nanochains have achieved effective absorption of electromagnetic waves in the frequency range of 6–14 GHz when the thickness varies from 1.5 to 2.5 mm. Moreover, the reflection loss reaches −40 dB when the thickness is 2 mm, indicating that the absorption rate is almost 100%. Composite materials of iron nanoparticles and carbon nanotubes have a better absorption performance in low frequency range (2.36–7.8 GHz). Iron nanochains are expected to become an excellent absorbent with strong absorption ability, wide band, small thickness and low cost. Composite materials of iron nanoparticles and carbon nanotubes are expected to be a light absorbent with good absorption of S and C bands (2–8 GHz, IEEE Std 521TM-2002). By analyzing the relationship between attenuation constant, impedance matching, and reflection loss, we verified that for optimal absorption, the attenuation constant and the impedance matching must be perfectly matched. © 2018 Elsevier Lt

Electrostatic Force between Two Dielectric Particles in Electrorheological Fluids: beyond Spherical Particles

In an effort to increase the shear yield stress of dielectric electrorheological fluids, we focus on the electrostatic force of different forms of particles in a dielectric polarization model. By solving Laplace‘s equation and applying the multiple image method and the finite element method, the analytical and numerical solutions of the electrostatic force of a two-sphere structure have been studied. The results suggest that when the dielectric mismatch factor is large and when the positions of the two spheres are nearly in contact with each other, most of the analytical solutions either over-or underestimate the force. Additionally, the structure of particles beyond the spherical form is considered. Three example cases are studied to shed light on how different geometries of particles may affect the electrostatic force, thereby influencing the shear yield stress of the fluid

Electrostatic Force between Two Dielectric Particles in Electrorheological Fluids: beyond Spherical Particles

In an effort to increase the shear yield stress of dielectric electrorheological fluids, we focus on the electrostatic force of different forms of particles in a dielectric polarization model. By solving Laplace‘s equation and applying the multiple image method and the finite element method, the analytical and numerical solutions of the electrostatic force of a two-sphere structure have been studied. The results suggest that when the dielectric mismatch factor is large and when the positions of the two spheres are nearly in contact with each other, most of the analytical solutions either over-or underestimate the force. Additionally, the structure of particles beyond the spherical form is considered. Three example cases are studied to shed light on how different geometries of particles may affect the electrostatic force, thereby influencing the shear yield stress of the fluid

Electrospinning fabrication of polystyrene-silica hybrid fibrous membrane for high-efficiency air filtration

International audienceThe development of new materials for air filtration and particulate matter (PM) pollution is critical to solving global environmental issues that threaten human health and accelerate the greenhouse effect. In this study, a novel electrospun polystyrene-SiO 2 nanoparticle (PS-SNP) fibrous membrane was explored by a single-step strategy to obtain the composite multi-layered filter masks. In addition, the air filtration performance of this fibrous membrane for PM was evaluated. The effects of SiO 2 on the composition, morphology, mechanical property, and surface wetting of PS-SNP membranes were studied. Allowing SiO 2 to be incorporated into the PS polymer was endowed with promising superhydrophobicity and demonstrated excellent mechanical properties. As-prepared PS-SNP membranes possess significantly better filtration efficiency than pure PS membrane. Furthermore, a three-layered air filter media (viscose/PS-SNP/polyethylene terephthalate) used in this study has considerable performances compared to the commercial masks. Since this air filtration membrane has excellent features such as high air filtration and permeability, we anticipate it to have huge potential application in air filtration systems, including cleanroom, respirator, and protective clothing