12 research outputs found
Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System
The glymphatic system (GS) hypothesis states that advective driven cerebrospinal fluid (CSF) influx from the perivascular spaces into the interstitial fluid space rapidly transport solutes and clear waste from brain. However, the presence of advection in neuropil is contested and solutes are claimed to be transported by diffusion only. To address this controversy, we implemented a regularized version of the optimal mass transport (rOMT) problem, wherein the advection/diffusion equation is the only a priori assumption required. rOMT analysis with a Lagrangian perspective of GS transport revealed that solute speed was faster in CSF compared to grey and white matter. Further, rOMT analysis also demonstrated 2-fold differences in regional solute speed within the brain. Collectively, these results imply that advective transport dominates in CSF while diffusion and advection both contribute to GS transport in parenchyma. In a rat model of cerebral small vessel disease (cSVD), solute transport in the perivascular spaces (PVS) and PVS-to-tissue transfer was slower compared to normal rats. Thus, the analytical framework of rOMT provides novel insights in the local dynamics of GS transport that may have implications for neurodegenerative diseases. Future studies should apply the rOMT analysis approach to confirm GS transport reductions in humans with cSVD
Genotypic and Environmental Variations in Grain Cadmium and Arsenic Concentrations Among a Panel of High Yielding Rice Cultivars
Genotypic and Environmental Variations in Grain Cadmium and Arsenic Concentrations Among a Panel of High Yielding Rice Cultivars
Abstract Background Rice is a major dietary source of cadmium (Cd) and arsenic (As) for populations consuming rice as the staple food. Excessive Cd and As accumulation in rice grain is of great concern worldwide, especially in South China where soil contamination with heavy metals and metalloids is widespread. It is important to reduce Cd and As accumulation in rice grain through selection and breeding of cultivars accumulating low levels of Cd or As. Results To assess the genetic and environmental variations in the concentrations of Cd and As in rice grains, 471 locally adapted high-yielding rice cultivars were grown at three moderately contaminated sites in South China for two years. Cadmium and As concentrations in brown rice varied by 10 – 32 and 2.5 – 4 fold, respectively. Genotype (G), environment (E) and G x E interactions were highly significant factors explaining the variations. Brown rice Cd concentration was found to correlate positively with the heading date among different cultivars, whereas As concentration and heading date correlated negatively. There was a significant and negative correlation between grain Cd and As concentrations. Conclusions Eight and 6 rice cultivars were identified as stable low accumulators of Cd and As, respectively, based on the multiple site and season trials. These cultivars are likely to be compliant with the grain Cd or As limits of the Chinese Food Safety Standards when grown in moderately contaminated paddy soils in South China
Two regional ventilation–perfusion patterns of lung consolidation assessed by electrical impedance tomography and ultrasound
Metal-Chelating Polymers (MCPs) with Zwitterionic Pendant Groups Complexed to Trastuzumab Exhibit Decreased Liver Accumulation Compared to Polyanionic MCP Immunoconjugates
Metal-chelating polymers (MCPs) can
amplify the radioactivity delivered
to cancer cells by monoclonal antibodies or their Fab fragments. We
focus on trastuzumab (tmAb), which is used to target cancer cells
that overexpress human epidermal growth factor receptor 2 (HER2).
We report the synthesis and characterization of a biotin (Bi) end-capped
MCP, Bi-PAmÂ(DET-DTPA)<sub>36</sub>, a polyacrylamide with diethylenetriaminepentaacetic
acid (DTPA) groups attached as monoamides to the polymer backbone
by diethylenetriamine (DET) pendant groups. We compared its behavior
in vivo and in vitro to a similar MCP with ethylenediamine (EDA) pendant
groups (Bi-PAmÂ(EDA-DTPA)<sub>40</sub>). These polymers were complexed
to a streptavidin-modified Fab fragment of tmAb, then labeled with <sup>111</sup>In to specifically deliver multiple copies of <sup>111</sup>In to HER2+ cancer cells. Upon decay, <sup>111</sup>In emits γ-rays
that can be used in single-photon emission computed tomography radioimaging,
as well as Auger electrons that cause lethal double strand breakage
of DNA. Our previous studies in Balb/c mice showed that radioimmunoconjugates
(RICs) containing the Bi-PAmÂ(EDA-DTPA)<sub>40</sub> polymer had extremely
short blood circulation time and high liver uptake and were, thus,
unsuitable for in vivo studies. The polymer Bi-PAmÂ(EDA-DTPA)<sub>40</sub> carries negative charges on each pendant group at neutral pH and
a net charge of (−1) on each pendant group when saturated with
stable In<sup>3+</sup>. To test our hypothesis that charge associated
with the polymer repeat unit is a key factor affecting its biodistribution
profile, we examined the biodistribution of RICs containing Bi-PAmÂ(DET-DTPA)<sub>36</sub>. While this polymer is also negatively charged at neutral
pH, it becomes a zwitterionic MCP upon saturation of the DTPA groups
with stable In<sup>3+</sup> ions. In both nontumor bearing Balb/c
mice and athymic mice implanted with HER2+ SKOV-3 human ovarian cancer
tumors, we show that the zwitterionic MCP has improved biodistribution,
higher blood levels of radioactivity, lower levels of normal tissue
uptake, and higher tumor uptake. Surface plasmon resonance experiments
employing the extracellular domain of HER2 show that the MCP immunoconjugates
retain high affinity antigen recognition, with dissociation constants
in the low nM range. In vitro studies with SKOV-3 cells for both MCP
immunoconjugates show a combination of specific binding that can be
completed in the presence of excess tmAb IgG and nonspecific binding
(NSB) that persists in the presence of tmAb IgG. We conclude that
zwitterionic MCPs represent a much better choice than polymers with
charges along the backbone for in vivo delivery of RICs to HER2+ cancer
cells
Additional file 2: of Genotypic and Environmental Variations in Grain Cadmium and Arsenic Concentrations Among a Panel of High Yielding Rice Cultivars
Boxplots of grain Cd and As concentrations of different rice subgroups, and correlation of grain As and Cd concentrations and with grain yield respectively. (DOCX 251 kb
Effect of Bufei granule on stable chronic obstructive pulmonary disease: a randomized, double blinded, placebo-controlled, and multicenter clinical study
Nanopore-based Fourth-generation DNA Sequencing Technology
Nanopore-based sequencers, as the fourth-generation DNA sequencing technology, have the potential to quickly and reliably sequence the entire human genome for less than 100. The single-molecule techniques used by this technology allow us to further study the interaction between DNA and protein, as well as between protein and protein. Nanopore analysis opens a new door to molecular biology investigation at the single-molecule scale. In this article, we have reviewed academic achievements in nanopore technology from the past as well as the latest advances, including both biological and solid-state nanopores, and discussed their recent and potential applications