Solution structure of the N‐terminal domain of DC‐UbP/UBTD2 and its interaction with ubiquitin

DC‐UbP/UBTD2 is a ubiquitin (Ub) domain‐containing protein first identified from dendritic cells, and is implicated in ubiquitination pathway. The solution structure and backbone dynamics of the C‐terminal Ub‐like (UbL) domain were elucidated in our previous work. To further understand the biological function of DC‐UbP, we then solved the solution structure of the N‐terminal domain of DC‐UbP (DC‐UbP_N) and studied its Ub binding properties by NMR techniques. The results show that DC‐UbP_N holds a novel structural fold and acts as a Ub‐binding domain (UBD) but with low affinity. This implies that the DC‐UbP protein, composing of a combination of both UbL and UBD domains, might play an important role in regulating protein ubiquitination and delivery of ubiquitinated substrates in eukaryotic cells.     

Primate stem cells: bridge the translation from basic research to clinic application

A growing body of literature has shown that stem cells are very effective for the treatment of degenerative diseases in rodents but these exciting results have not translated to clinical practice. The difference results from the divergence in genetic, metabolic, and physiological phenotypes between rodents and humans. The high degree of similarity between non-human primates(NHPs) and humans provides the most accurate models for preclinical studies of stem cell therapy. Using a NHP model to understand the following key issues, which cannot be addressed in humans or rodents, will be helpful for extending stem cell applications in the basic science and the clinic. These issues include pluripotency of primate stem cells, the safety and efficiency of stem cell therapy, and transplantation procedures of stem cells suitable for clinical translation. Here we review studies of the above issues in NHPs and current challenges of stem cell applications in both basic science and clinical therapies. We propose that the use of NHP models, in particular combining the serial production and transplantation procedures of stem cells is the most useful for preclinical studies designed to overcome these challenges.     

Modulatory effect of Lactobacillus acidophilus KLDS 1.0738 on intestinal short‐chain fatty acids metabolism and GPR41/43 expression in β‐lactoglobulin–sensitized mice

We investigated the correlation between the beneficial effect of Lactobacillus acidophilus on gut microbiota composition, metabolic activities, and reducing cow's milk protein allergy. Mice sensitized with β‐lactoglobulin (β‐Lg) were treated with different doses of L. acidophilus KLDS 1.0738 for 4 weeks, starting 1 week before allergen induction. The results showed that intake of L. acidophilus significantly suppressed the hypersensitivity responses, together with increased fecal microbiota diversity and short‐chain fatty acids (SCFAs) concentration (including propionate, butyrate, isobutyrate, and isovalerate) when compared with the allergic group. Moreover, treatment with L. acidophilus induced the expression of SCFAs receptors, G‐protein–coupled receptors 41 (GPR41) and 43 (GPR43), in the spleen and colon of the allergic mice. Further analysis revealed that the GPR41 and GPR43 messenger RNA expression both positively correlated with the serum concentrations of transforming growth factor‐β and IFN‐γ (p < .05), but negatively with the serum concentrations of IL‐17, IL‐4, and IL‐6 in the L. acidophilus–treated group compared with the allergic group (p < .05). These results suggested that L. acidophilus protected against the development of allergic inflammation by improving the intestinal flora, as well as upregulating SCFAs and their receptors GPR41/43.     

Comparison of the expression of cell surface poly-N-acetyllactosamine-type oligosaccharides in PC12 cells with those in its variant PC12D.

To explore the biological role of carbohydrate chains in the process of nerve cell differentiation, we carried out a characterization of the carbohydrate structure of glycoproteins by comparing conventional PC12 cells with variant cells (PC12D). In vitro metabolic labeling of cells with either [(3)H] glucosamine or [(3)H] threonine, together with tomato lectin staining, revealed that nerve growth factor (NGF) stimulation caused a decrease in the poly-N-acetyllactosamine synthesis of high-molecular-weight glycopeptides from PC12 cells. By comparison, the amount of glycopeptides with poly-N-acetyllactosamine from PC12D cells was already significantly low and it was not changed by NGF stimulation. By assaying the glycosyltransferases that participate in poly-N-acetyllactosamine synthesis, the decrease in the amount of the poly-N-acetyllactosamine in PC12D cells as well as NGF-stimulated PC12 cells could be accounted for by a reduction in the activity of poly-N-acetyllactosamine extension enzyme (GnT-i), because the amount of poly-N-acetyllactosamine in both cells precisely correlated with changes in GnT-i activity, whereas the activities of N-acetylglucosaminyltransferase V (GnT-V) and beta 1-4 galactosyltransferase remained unchanged. These results demonstrate that the decrease in poly-N-acetyllactosamine synthesis in PC12 cells occurred prior to neurite formation, whereas PC12D cells were insensitive to this effect. Next, we showed that GnT-i but not GnT-V catalyzed a rate-limiting reaction in the expression of poly-N-acetyllactosamine chains, especially in pheochromocytoma.     

Statistical Mechanics of Zooplankton

Statistical mechanics provides the link between microscopic properties of many-particle systems and macroscopic properties such as pressure and temperature. Observations of similar “microscopic” quantities exist for the motion of zooplankton, as well as many species of other social animals. Herein, we propose to take average squared velocities as the definition of the “ecological temperature” of a population under different conditions on nutrients, light, oxygen and others. We test the usefulness of this definition on observations of the crustacean zooplankton Daphnia pulicaria. In one set of experiments, D. pulicaria is infested with the pathogen Vibrio cholerae, the causative agent of cholera. We find that infested D. pulicaria under light exposure have a significantly greater ecological temperature, which puts them at a greater risk of detection by visual predators. In a second set of experiments, we observe D. pulicaria in cold and warm water, and in darkness and under light exposure. Overall, our ecological temperature is a good discriminator of the crustacean’s swimming behavior.     

The role of tropomyosin in the interactions of F-actin with caldesmon and actin-binding protein (or filamin)

The interactions of actin filaments with actin-binding protein (filamin) and caldesmon under the influence of tropomyosin were studied in detail using falling-ball viscometry, binding assay and electron microscopy. Caldesmon decreased the binding constant of filamin with F-actin. In contrast, the maximum binding ability of filamin to F-actin was decreased by tropomyosin. The filamin-induced gelation of actin filaments was inhibited by caldesmon. Tropomyosin also inhibited this gelation. The effect of caldesmon became stronger under the influence of tropomyosin. Furthermore, both caldesmon and tropomyosin additionally decreased the filamin binding to F-actin. From these results, caldesmon and tropomyosin appeared to influence filamin binding to F-actin with different modes of actin. In addition, there was no sign of direct interactions between filamin, caldesmon and tropomyosin as judged from gel filtration. Under the influence of caldesmon and tropomyosin, calmodulin conferred Ca2+ sensitivity on the filamin-induced gelation of actin filaments.     

Hyperplastic cellular components of a hemangiopericytoma. An ultrastructural study

Based on ultrastructural features of cellular components of a hemangiopericytoma, hyperplastic cells are classifiable into fibroblast-like (group I), endotheloid (group II) and pericyte-like (group III) cells. The transformation of the group I cells to the group II, or to the group III cells, is pronounced in our electron micrographs and this may imply that the group I cell is the principal cell of origin in this neoplasm. The smooth muscle-like (group IV) cells comprising the media of the arteries and veins in this neoplasm may represent modified, possibly de-differentiated smooth muscle cells reacted to the neoplastic proliferation of the surrounding adventitial (group I) cells.