Margination and adhesion dynamics of tumor cells in a real microvascular network

In tumor metastasis, the margination and adhesion of tumor cells are two critical and closely related steps, which may determine the destination where the tumor cells extravasate to. We performed a direct three-dimensional simulation on the behaviors of the tumor cells in a real microvascular network, by a hybrid method of the smoothed dissipative particle dynamics and immersed boundary method (SDPD-IBM). The tumor cells are found to adhere at the microvascular bifurcations more frequently, and there is a positive correlation between the adhesion of the tumor cells and the wall-directed force from the surrounding red blood cells (RBCs). The larger the wall-directed force is, the closer the tumor cells are marginated towards the wall, and the higher the probability of adhesion behavior happen is. A relatively low or high hematocrit can help to prevent the adhesion of tumor cells, and similarly, increasing the shear rate of blood flow can serve the same purpose. These results suggest that the tumor cells may be more likely to extravasate at the microvascular bifurcations if the blood flow is slow and the hematocrit is moderate.     

The Role of Host Cytoskeleton in Flavivirus Infection

The family of flaviviruses is one of the most medically important groups of emerging arthropod-borne viruses. Host cell cytoskeletons have been reported to have close contact with flaviviruses during virus entry, intracellular transport, replication, and egress process, although many detailed mechanisms are still unclear. This article provides a brief overview of the function of the most prominent flaviviruses-induced or-hijacked cytoskeletal structures including actin, microtubules and intermediate filaments, mainly focus on infection by dengue virus, Zika virus and West Nile virus. We suggest that virus interaction with host cytoskeleton to be an interesting area of future research.     

Construction and Characterization of a CTLA-4-Targeted scFv–Melittin Fusion Protein as a Potential Immunosuppressive Agent for Organ Transplant

Immunotoxins with selective cytotoxicity are frequently used as therapeutic immunosuppressive agents in solid-organ transplantation because of their efficiency and high specificity. In this study, we present a new recombinant immunotoxin termed anti-CTLA-4-scFv–melittin prepared from Escherichia coli aimed at clearing activated T cells at the same time avoiding all-round decline in systematic immunity. This fusion protein is composed of anti-CTLA-4-scFv unit and melittin analog unit with properties of low immunogenicity and selective cytotoxicity to CTLA-4-positive T cells. In preliminary biological activity assays, our results confirmed the feasibility of activated T cell clearance strategy and there were significant differences in cell survival rates between CTLA-4-positive group and control group at all experimental concentrations of the immunotoxin. The selective cytotoxicity, low immunogenicity, and low production cost make it an attractive alternate to traditional immunosuppressants.     

Yaks and sheep trigger different changes in the grasshopper assemblages of the Qilian Mountains via differentially altering plant assemblages

1. The Qilian Mountains represent one of the key livestock‐raising grasslands in China. The two main herbivore species raised in this area – yaks and sheep – are of critical economical value. Grasshoppers compete with these animals for available nutrients, creating multifaceted relationships between livestock, grasshoppers and plants. A clear understanding of such relationships is lacking and is urgently needed to guide conservation efforts. 2. This study aims to document the effects of yak and sheep grazing on grasshopper assemblages and to elucidate the underlying mechanisms of such effects. 3. It is shown here that yaks and sheep impact grasshopper assemblages differently. Grasshopper assemblages exhibited lower density, biodiversity, richness, and evenness of distribution in yak‐grazed pastures than in grazing‐free grasslands. Sheep‐grazed pastures exhibited a dramatically divergent picture, with elevated density, biodiversity and richness, and a slightly decreased evenness of distribution. Grasshoppers were generally larger in grazed pastures than in grazing‐free grasslands, especially in yak‐grazed plots. 4. The present study suggests that differences between yak and sheep pastures in plant assemblage structure and plant traits are probably the underlying forces driving the differences in grasshopper assemblage structure and grasshopper traits, respectively. 5. The study shows that the grasshopper habitat indicator species differ between yak and sheep pastures, raising the possibility that such indicators can be used to monitor grassland usage and degradation in the Qilian Mountains. 6. These results provide novel insights into the dynamic interactions of common domesticated herbivore species, grasshoppers and plants in Qilian Mountains, which augment current knowledge and may ultimately lead to better conservation practices.     

U-Shape Suppressive Effect of Phenol Red on the Epileptiform Burst Activity via Activation of Estrogen Receptors in Primary Hippocampal Culture

Phenol red is widely used in cell culture as a pH indicator. Recently, it also has been reported to have estrogen-like bioactivity and be capable of promoting cell proliferation in different cell lines. However, the effect of phenol red on primary neuronal culture has never been investigated. By using patch clamp technique, we demonstrated that hippocampal pyramidal neurons cultured in neurobasal medium containing no phenol red had large depolarization-associated epileptiform bursting activities, which were rarely seen in neurons cultured in phenol red-containing medium. Further experiment data indicate that the suppressive effect of the phenol red on the abnormal epileptiform burst neuronal activities was U-shape dose related, with the most effective concentration at 28 µM. In addition, this concentration related inhibitory effect of phenol red on the epileptiform neuronal discharges was mimicked by 17-β-estradiol, an estrogen receptor agonist, and inhibited by ICI-182,780, an estrogen receptor antagonist. Our results suggest that estrogen receptor activation by phenol red in the culture medium prevents formation of abnormal, epileptiform burst activity. These studies highlight the importance of phenol red as estrogen receptor stimulator and cautions of careful use of phenol red in cell culture media.     

SOME REMARKS ON CHENJIAWO FAUNA──On the First Appearance of Peking Man Fauna

I.CORRELATIONBETWEENL0ESSSECTI0NAND0XYGENIS0TOPESTAGESIntheYuanloessarea,manyscientiststhinkthatthesedimentsarecontinuousandtheclimaticrecordsareperfect.Thisdoesnotappeartobeaccurate.Sedimentationwasdiscontinuousinmanysections.Forexample,manyscientistsarguethatS2corresp0ndstooxygenisot0peStage7(Liu,l985,KuklaandAn,l989;Dingetal.,l990).lnfact,S2includesthreelayersfS2SSl,S2LLlandS2SS2.Dingetal.(l990)reportedthatthereisathickunitofloessbetweenS2SSlandS2SS2intheBaicao…     

Modulation by polyelectrolytes of canine cardiac microsomal calcium uptake and the possible relationship to phospholamban

Calcium uptake and (Ca2+ + Mg2+)-ATPase activity in canine cardiac microsomes were found to be stimulated by heparin and various other polyanions. Prior treatment of the microsomes with the ionophores alamethicin or A23187 produced no change in the extent of stimulation of the ATPase activity by heparin yet eliminated net calcium uptake. This finding and a lack of change in the stoichiometric ratio of mol of calcium transported/mol of ATP hydrolyzed (calcium:ATP) suggest that the effect of heparin is on the calcium pump rather than on a parallel calcium efflux pathway. Certain polycationic compounds including poly-L-arginine and histone inhibited both cardiac and fast skeletal muscle microsomal calcium uptake and also produced no change in the stoichiometric ratio of calcium to ATP. Several lines of evidence indicate that the polyanionic compounds tested stimulate calcium uptake by interacting with phospholamban, the putative phosphorylatable regulator of the cardiac sarcoplasmic reticulum calcium pump, whereas polycationic compounds appear to interact with the pump. (i) Heparin stimulated calcium uptake to the same extent as protein kinase A or trypsin, whereas prior phosphorylation or tryptic cleavage of phospholamban from the membrane abolished the stimulatory effect of heparin. (ii) Calcium uptake and (Ca2+ + Mg2+)-ATPase activity in fast skeletal muscle microsomes, which lack phospholamban, were unaffected by heparin. (iii) Purified cardiac (Ca2+ + Mg2+)-ATPase activity was no longer stimulated by heparin yet was still inhibited by polycationic compounds. The heparin-induced stimulation of calcium uptake was dependent on the pH and ionic strength of the heparin-containing preincubation medium, hence electrostatic interactions appear to play a significant role in heparin's stimulatory action. The data are consistent with an inhibitory role of the positively charged cytoplasmic domain of phospholamban with respect to calcium pump activity and the relief of the inhibition upon reduction in phospholamban's positive charge by phosphorylation or binding of polyanions.