Structural and thermodynamic characterization of the self-adhesive properties of human P-cadherin

Human P-cadherin is a promising therapeutic target against cancer. However, its characterization at the molecular level is still lacking. We report that human P-cadherin associated irreversibly in a distinct dimer configuration. Unexpectedly, the divalent cation Ca2? was not necessary for dimerization, although it greatly stabilized the protein-protein complex.     

Cryo-EM structure of monomeric photosystem II at 2.78 Å resolution reveals factors important for the formation of dimer

Photosystem II (PSII) functions mainly as a dimer to catalyze the light energy conversion and water oxidation reactions. However, monomeric PSII also exists and functions in vivo in some cases. The crystal structure of monomeric PSII has been solved at 3.6 Å resolution, but it is still not clear which factors contribute to the formation of the dimer. Here, we solved the structure of PSII monomer at a resolution of 2.78 Å using cryo-electron microscopy (cryo-EM). From our cryo-EM density map, we observed apparent differences in pigments and lipids in the monomer-monomer interface between the PSII monomer and dimer. One β-carotene and two sulfoquinovosyl diacylglycerol (SQDG) molecules are found in the monomer-monomer interface of the dimer structure but not in the present monomer structure, although some SQDG and other lipid molecules are found in the analogous region of the low-resolution crystal structure of the monomer, or cryo-EM structure of an apo-PSII monomer lacking the extrinsic proteins from Synechocystis sp. PCC 6803. In the current monomer structure, a large part of the PsbO subunit was also found to be disordered. These results indicate the importance of the β-carotene, SQDG and PsbO in formation of the PSII dimer.     

Enhanced Expression of an Endothelin ETA Receptor in Capillaries from Human Glioblastoma: A Quantitative Receptor Autoradiographic Analysis Using a Radioluminographic Imaging Plate System

Abstract: We identified and characterized ¹²⁵I-endothelin-1 (¹²⁵I-ET-1) binding sites in tumor capillaries isolated from human glioblastomas, using the quantitative receptor autoradiographic technique with pellet sections. Quantification was done using the computerized radioluminographic imaging plate system. High-affinity ET receptors were localized in capillaries from glioblastomas and the surrounding brain tissues (K_D = 4.7 ± 1.0 × 10^?10 and 1.6 ± 0.3 × 10^?10M, respectively; B_max = 161 ± 38 and 140 ± 37 fmol/mg, respectively; mean ± SEM, n = 5). BQ-123, a selective antagonist for the ET_A receptor, potently competed for ¹²⁵I-ET-1 binding to sections of the microvessels with IC₅₀ values of 5.1 ± 0.3 and 5.1 ± 1.5 nM, and 10^?6M BQ-123 displaced 84 and 58% of ET binding to capillaries from tumors and brains, respectively. In addition, competition curves obtained in the presence of increasing concentrations of ET-3 showed two components (IC₅₀ = 5.7 ± 2.5 × 10^?10 and 1.4 ± 0.2 × 10^?6M for tumor microvessels, 1.8 ± 0.6 × 10^?10 and 1.1 ± 0.3 × 10^?6M for brain microvessels, respectively). Our results indicate that (a) the method we used is simple and highly sensitive for detecting and characterizing various receptors in tumor capillaries, especially in the case of a sparse specimen, and (b) capillaries in glioblastomas express specific high-affinity ET binding sites, candidates for biologically active ET receptors, which predominantly belong to the ET_A subtype.     

Protection of Coral Larvae from Thermally Induced Oxidative Stress by Redox Nanoparticles

Coral reefs are one of the most biologically diverse and economically important ecosystems on earth. However, the destruction of coral reefs has been reported worldwide owing to rising seawater temperature associated with global warming. In this study, we investigated the potential of a redox nanoparticle (RNP^O) to scavenge reactive oxygen species (ROS), which are overproduced under heat stress and play a crucial role in causing coral mortality. When reef-building coral (Acropora tenuis) larvae, without algal symbionts, were exposed to thermal stress at 33 °C, RNP^O treatment significantly increased the survival rate. Proteome analysis of coral larvae was performed using nano-liquid chromatography-tandem mass spectrometry for the first time. The results revealed that several proteins related to ROS-induced oxidative stress were specifically identified in A. tenuis larvae without RNP^O treatment, whereas these proteins were absent in RNP^O-treated larvae, which suggested that RNP^O effectively scavenged ROS from A. tenuis larvae. Results from this study indicate that RNP^O treatment can reduce ROS in aposymbiotic coral larvae and would be a promising approach for protecting corals from thermal stress.     

Focus: Zoonotic Disease: New Series of Imidazoles Showed Promising Growth Inhibitory and Curative Potential Against Trypanosoma Infection

The Trypanosoma spp. cause animal and human trypanosomiasis characterized with appreciable health and economic burden mostly in developing nations. There is currently no effective therapy for this parasitic disease, due to poor drug efficacy, drug resistance, and unwanted toxicity, etc. Therefore, new anti-Trypanosoma agents are urgently needed. This study explored new series of imidazoles for anti-Trypanosoma properties in vitro and in vivo. The imidazoles showed moderate to strong and specific action against growth of T. congolense. For example, the efficacy of the imidazole compounds to restrict Trypanosoma growth in vitro was ≥ 12-fold specific towards T. congolense relative to the mammalian cells. Additionally, the in vivo study revealed that the imidazoles exhibited promising anti-Trypanosoma efficacy corroborating the in vitro anti-parasite capacity. In particular, three imidazole compounds (C1, C6, and C8) not only cleared the systemic parasite burden but cured infected rats after no death was recorded. On the other hand, the remaining five imidazole compounds (C2, C3, C4, C5, and C7) drastically reduced the systemic parasite load while extending survival time of the infected rats by 14 days as compared with control. Untreated control died 3 days post-infection, while the rats treated with diminazene aceturate were cured comparable to the results obtained for C1, C6, and C8. In conclusion, this is the first study demonstrating the potential of these new series of imidazoles to clear the systemic parasite burden in infected rats. Furthermore, a high selectivity index of imidazoles towards T. congolense in vitro and the oral LD₅₀ in rats support anti-parasite specific action. Together, findings support the anti-parasitic prospects of the new series of imidazole derivatives.     

Do gravid females become selfish? Female allocation of energy during gestation

Net energy availability depends on plasma corticosterone concentrations, food availability, and their interaction. Limited net energy availability requires energy trade-offs between self-maintenance and reproduction. This is important in matrotrophic viviparous animals because they provide large amounts of energy for embryos, as well as self-maintenance, for the extended period of time during gestation. In addition, gravid females may transmit environmental information to the embryos in order to adjust offspring phenotype. We investigated effects of variation in maternal plasma corticosterone concentration and maternal food availability (2 × 2 factorial design) during gestation on offspring phenotype in a matrotrophic viviparous lizard (Pseudemoia entrecasteauxii). Subsequently, we tested preadaptation of offspring phenotype to their postnatal environment by measuring risk-averse behavior and growth rate using reciprocal transplant experiments. We found that maternal net energy availability affected postpartum maternal body condition, offspring snout-vent length, offspring mass, offspring performance ability, and offspring fat reserves. Females treated with corticosterone allocated large amounts of energy to their own body condition, and their embryos allocated more energy to energy reserves than somatic growth. Further, offspring from females in high plasma corticosterone concentration showed compensatory growth. These findings suggest that while females may be selfish when gestation conditions are stressful, the embryos may adjust their phenotype to cope with the postnatal environment.