Adenylate cyclase activity of membrane fractions isolated from sea urchin sperm

The adenylate cyclase activity of sperm membrane fragments isolated from Lytechinus pictus sperm according to Cross [20] has been studied. Two distinct fractions preferentially coming from the flagellar plasma membrane are obtained. Surface I¹²⁵-labeling experiments performed by Cross [20] indicate that these membranes are representative of the entire sperm plasma membrane. Both fractions are enriched in their adenylate cyclase activity: the specific activity of the top membranes is eightfold higher than in whole sperm, whereas that of the middle membranes is 15-fold higher. The cyclase seems to be associated with the membranes. Lytechinus pictus egg jelly has no effect or slightly inhibits the adenylate cyclase activity of the isolated sperm plasma membrane fragments. Mg⁺⁺ and Na⁺ stimulated their cyclase activity about sevenfold at 2.5 mM Mn⁺⁺ and 3.2 mM ATP. At this ATP to Mn⁺⁺ ratio, high concentrations of Ca⁺⁺ have a small stimulatory effect.     

Rapid ligand-regulated gating kinetics of single inositol 1,4,5-trisphosphate receptor Ca2+ release channels

The ubiquitous inositol 1,4,5-trisphosphate receptor (InsP(3)R) intracellular Ca(2+) release channel is engaged by thousands of plasma membrane receptors to generate Ca(2+) signals in all cells. Understanding how complex Ca(2+) signals are generated has been hindered by a lack of information on the kinetic responses of the channel to its primary ligands, InsP(3) and Ca(2+), which activate and inhibit channel gating. Here, we describe the kinetic responses of single InsP(3)R channels in native endoplasmic reticulum membrane to rapid ligand concentration changes with millisecond resolution, using a new patch-clamp configuration. The kinetics of channel activation and deactivation showed novel Ca(2+) regulation and unexpected ligand cooperativity. The kinetics of Ca(2+)-mediated channel inhibition showed the single-channel bases for fundamental Ca(2+) release events and Ca(2+) release refractory periods. These results provide new insights into the channel regulatory mechanisms that contribute to complex spatial and temporal features of intracellular Ca(2+) signals.     

Mathematical model of a personalized neoantigen cancer vaccine and the human immune system

Cancer vaccines are an important component of the cancer immunotherapy toolkit enhancing immune response to malignant cells by activating CD4⁺ and CD8⁺ T cells. Multiple successful clinical applications of cancer vaccines have shown good safety and efficacy. Despite the notable progress, significant challenges remain in obtaining consistent immune responses across heterogeneous patient populations, as well as various cancers. We present a mechanistic mathematical model describing key interactions of a personalized neoantigen cancer vaccine with an individual patient’s immune system. Specifically, the model considers the vaccine concentration of tumor-specific antigen peptides and adjuvant, the patient’s major histocompatibility complexes I and II copy numbers, tumor size, T cells, and antigen presenting cells. We parametrized the model using patient-specific data from a clinical study in which individualized cancer vaccines were used to treat six melanoma patients. Model simulations predicted both immune responses, represented by T cell counts, to the vaccine as well as clinical outcome (determined as change of tumor size). This model, although complex, can be used to describe, simulate, and predict the behavior of the human immune system to a personalized cancer vaccine.     

Chiral bimetallic complexes from chiral salen metal complexes and mercury (II) halides and acetates: the anionic groups interact with Cu(II) in apical position

A series of chiral bimetallic complexes have been prepared containing both Cu(II) and Hg(II) metal centers. The complexes possess chiral salen ligands which host Cu(II) in the center of the cis-N₂O₂ chromophore and Hg(II) via two oxygen atoms of the chromophore. Halogen and acetate groups from mercury salts interact with the Cu(II) center. The X-ray crystallographic data of 11 reveals a short distance of Cl?Cu (3.22-3.26 Å). EPR study also discloses a strong interaction, in particular, of acetate group with Cu.     

Pollination features and floral volatiles of Gymnospermium scipetarum (Berberidaceae)

Journal of Plant Research - The discovery of few isolated populations of Gymnospermium scipetarum (since now considered as an amphi-Adriatic endemic) in the S-Apennines prompted to investigate,...     

Effect of rioprostil and colchicine on CC14-acute liver damage in rats. Relationship with plasma membrane lipids

The effects of colchicine (10 g/day p.o. for 7 days) and rioprostil (2-decarboxy, 2-hydroxymethyl-15-deoxy-16-RS-hydroxy-16-methyl-prostaglandin-E1) (20 g/kg s.c., a single dose) on the enzymatic and histological markers of acute liver damage were studied in rats intoxicated with a single oral dose of CC1₄. The rats were sacrificed 24 h after CC1₄. The lipid composition of the liver plasma membranes was also determined. The increase in Alk. Phosp., GGTP and GPT activities and bilirubin concentration in serum as well as the histological images produced by CC1₄ were equally prevented by the treatments with colchicine or rioprostil. CC1₄ changed the lipid composition of the liver plasma membrane by increasing PI and PC and decreasing SM, PS and PEA. There was a decrease in the cholesterol/phospholipid ratio at the expense of a reduction of cholesterol/protein ratio and elevation in phospholipid/protein ratio. Colchicine and rioprostil also prevented these lipid alterations. The results suggest that the plasma membrane is an important site of action of CC1₄ and of the 2 drugs studied. We postulate that the plasma membrane rather than other organelles is the target for the cytoprotective actions of prostaglandins.