Plant functional types and climatic change: Introduction

Abstract. Plant functional types are a necessary device for reducing the complex and often uncharted characteristics of species diversity in function and structure when attempting to project the nature and function of species assemblages into future environments. A workshop was held to review the current methods commonly used for defining plant functional types, either globally or for particular biomes, and to compare them with the field experiences of specialists for specific biomes of the world. The methods fall into either an objective and inductive approach or a subjective and deductive approach. When the different methods were tested, it was generally found that the classification for one site or environment was not wholly applicable to a different site or environment. However, the degree of change which is necessary for adjustment between environments may not prove to be a major limitation in the use of functional types.     

Distinctive communication networks in inactive states of β2-adrenergic receptor: Mutual information and entropy transfer analysis

Mutual information and entropy transfer analysis employed on two inactive states of human beta-2 adrenergic receptor (β₂-AR) unraveled distinct communication pathways. Previously, a so-called “highly” inactive state of the receptor was observed during 1.5 microsecond long molecular dynamics simulation where the largest intracellular loop (ICL3) was swiftly packed onto the G-protein binding cavity, becoming entirely inaccessible. Mutual information quantifying the degree of correspondence between backbone-C_α fluctuations was mostly shared between intra- and extra-cellular loop regions in the original inactive state, but shifted to entirely different regions in this latest inactive state. Interestingly, the largest amount of mutual information was always shared among the mobile regions. Irrespective of the conformational state, polar residues always contributed more to mutual information than hydrophobic residues, and also the number of polar-polar residue pairs shared the highest degree of mutual information compared to those incorporating hydrophobic residues. Entropy transfer, quantifying the correspondence between backbone-C_α fluctuations at different timesteps, revealed a distinctive pathway directed from the extracellular site toward intracellular portions in this recently exposed inactive state for which the direction of information flow was the reverse of that observed in the original inactive state where the mobile ICL3 and its intracellular surroundings drove the future fluctuations of extracellular regions.     

A novel Golgi mannosidase inhibitor: Molecular design,synthesis, enzyme inhibition,and inhibition of spheroid formation

Effective chemotherapy for solid cancers is challenging due to a limitation in permeation that prevents anticancer drugs from reaching the center of the tumor, therefore unable to limit cancer cell growth. To circumvent this issue, we planned to apply the drugs directly at the center by first collapsing the outer structure. For this, we focused on cell–cell communication (CCC) between N-glycans and proteins at the tumor cell surface. Mature N-glycans establish CCC; however, CCC is hindered when numerous immature N-glycans are present at the cell surface. Inhibition of Golgi mannosidases (GMs) results in the transport of immature N-glycans to the cell surface. This can be employed to disrupt CCC. Here, we describe the molecular design and synthesis of an improved GM inhibitor with a non-sugar mimic scaffold that was screened from a compound library. The synthesized compounds were tested for enzyme inhibition ability and inhibition of spheroid formation using cell-based methods. Most of the compounds designed and synthesized exhibited GM inhibition at the cellular level. Of those, AR524 had higher inhibitory activity than a known GM inhibitor, kifunensine. Moreover, AR524 inhibited spheroid formation of human malignant cells at low concentration (10 µM), based on the disruption of CCC by GM inhibition.     

Developmental pattern of the bony tentorium of spider monkeys (Ateles)

Based on their developmental patterns, the bony tentorium (BT) and bony falx (BF) of mammals can be classified into two types, the carnivoran type and the dolphin type. The former develops as part of the skull bones during the fetal period and is already completed at birth, while the latter is gradually formed by ossification in the tentorium cerebelli (TC) and falx cerebri (FC) during the course of aging. The BT of spider monkeys is assigned to the dolphin type.     

Site-Specific Structural Variations Accompanying Tubular Assembly of the HIV-1 Capsid Protein

The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent ¹⁵N and ¹³C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide ¹H nuclei, and quantitative measurements of site-specific ¹⁵N–¹⁵N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 3₁₀-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant.     

Ligand Independence of the T618I Mutation in the Colony-stimulating Factor 3 Receptor (CSF3R) Protein Results from Loss of O-Linked Glycosylation and Increased Receptor Dimerization

Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. These CSF3R mutations fall into two distinct categories: membrane-proximal mutations and truncation mutations. Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. CSF3R truncation mutations induce overexpression and ligand hypersensitivity of the receptor, likely because of the removal of motifs necessary for endocytosis and degradation. In contrast, little is known about the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia. In contrast with CSF3R truncation mutations, membrane-proximal mutations do not exhibit overexpression and are capable of signaling in the absence of ligand. We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. Mutation at these sites prevents O-glycosylation of CSF3R and increases receptor dimerization. This increased dimerization explains the ligand-independent activation of CSF3R membrane-proximal mutations. Cytokine receptor activation through loss of O-glycosylation represents a novel avenue of aberrant signaling. Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action.