Protein phosphatase 5 protects neurons against amyloid-β toxicity

Amyloid-β (Aβ) is thought to promote neuronal cell loss in Alzheimer's disease, in part through the generation of reactive oxygen species (ROS) and subsequent activation of mitogen-activated protein kinase (MAPK) pathways. Protein phosphatase 5 (PP5) is a ubiquitously expressed serine/threonine phosphatase which has been implicated in several cell stress response pathways and shown to inactivate MAPK pathways through key dephosphorylation events. Therefore, we examined whether PP5 protects dissociated embryonic rat cortical neurons in vitro from cell death evoked by Aβ. As predicted, neurons in which PP5 expression was decreased by small-interfering RNA treatment were more susceptible to Aβ toxicity. In contrast, over-expression of PP5, but not the inactive mutant, PP5(H304Q), prevented MAPK phosphorylation and neurotoxicity induced by Aβ. PP5 also prevented cell death caused by direct treatment with H₂O₂, but did not prevent Aβ-induced production of ROS. Thus, the neuroprotective effect of PP5 requires its phosphatase activity and lies downstream of Aβ-induced generation of ROS. In summary, our data indicate that PP5 plays a pivotal neuroprotective role against cell death induced by Aβ and oxidative stress. Consequently, PP5 might be an effective therapeutic target in Alzheimer's disease and other neurodegenerative disorders in which oxidative stress is implicated.     

4-1BB (CD137), an inducible costimulatory receptor,as a specific target for cancer therapy

Although considerable progress has been made in understanding how tumors evade immune surveillance, measures to counter the same have not kept pace with the advances made in designing effective strategies. 4-1BB (CD137; TNFRS9), an activation-induced costimulatory molecule, is an important regulator of immune responses. Targeting 4-1BB or its natural ligand 4-1BB ligand (4-1BBL) has important implications in many clinical conditions, including cancer. In-depth analysis revealed that 4-1BB-mediated anti-cancer effects are based on its ability to induce activation of cytotoxic T lymphocytes (CTL), and among others, high amounts of IFN-γ. In this review, we will discuss the various aspects of 4-1BB-mediated anti-tumor responses, the basis of such responses, and future directions. [BMB Reports 2014; 47(3): 122-129]     

Distribution of coelobites (cavity-dwellers) in coral rubble across the Florida Reef Tract

The interstices of coral rubble, the most common deposits of many reefs, provide extensive surfaces for a variety of sessile and vagile coelobites (cavity-dwellers). In the northern Florida Reef Tract there are at least 80 different sessile coelobites in coral rubble collected from 21 stations from in-shore lagoon to fore-reef, depth 40 meters. Three microzones of coelobites on the undersides of rubble were distinguished on the bases of their dominant community assemblages; algal microzone in the peripheral area, sponge-bryozoan microzone in the transitional area, and foraminiferal microzone in the central area. In the transect that extends some 6–7 km across the reef tract, the biomass is largest in the rubble of the shallow (1–3 m) shelf margin and it decreases shoreward and in deeper water; however, the maximum variety of species comes in the fore-reef at depths of about 20–30 m. Four coelobite zones are recognized in the reef transect based on distribution pattern and relative abundance of diagnostic species; 1) in-shore lagoon zone, 2) lagoon-reef zone, 3) marginal reef zone, and 4) fore-reef zone. Although this paper does not propose a comprehensive explanation for the distribution of coelobites, it does emphasize the importance of two factors that affect coelobite development and distribution: interstitial sediment as a negative (limiting) factor and flushing as a positive factor.     

Rapid transient expression of cholera toxin B subunit (CTB) in Nicotiana benthamiana

Cholera toxin B subunit (CTB) has the potential to be an effective adjuvant for mucosal vaccines because of its ability to increase antigen uptake and presentation by antigen-presenting cells through GM1-ganglioside binding. CTB has been produced using different recombinant protein expression systems. This study used the geminiviral replicon system to transiently express CTB in Nicotiana benthamiana. The plant-optimized CTB gene was cloned into a geminiviral vector and infiltrated into N. benthamiana leaves. The highest CTB protein level was observed on day 4 with approximately 4 μg/g fresh weight. The Western blot analysis using anti-CTB suggests assembly of CTB into oligomers. Based on the GM1-ELISA results, this CTB transiently expressed in plants showed biological activity for binding the intestinal epithelial cell membrane glycolipid receptor, GM1-glanglioside, which implies its potential as an adjuvant for mucosal vaccines.     

Computed insulin profiles for normalization of glycemia in diabetic patients

The objective of this preliminary study was to develop a new quantitative method of setting the initial insulin infusion patterns in treatment of diabetic patients. The method is based upon the mathematical estimation of the insulin profile required to maintain the glucose level within the normal range after glucose loading in diabetic patients. Using our previously developed equivalent circuit model of glucose kinetics and the reported data of an intravenous glucose tolerance test (IVGTT) in two groups of normal and diabetic patients, two important physiological parameters of the model (the peripheral tissue's insulin resistivity and the hepatic sensitivity to glucose level) were computed for two clinical groups. Then the insulin profile was obtained by computing the plasma insulin concentrations required to keep the total glucose utilization rate of the tissue and the liver in the diabetic group equal to that of the normal group. The simulation result indicated that the computed insulin profile produced a plasma glucose profile which was more closely matched to the normal group's glucose profile than with the case of emulating the normal group's insulin profile in the diabetic group.