An aqueous extract of Liu Wei Di Huang Wan alters the labeling of blood constituents with Technetium-99m

The Liu Wei Di Huang Wan is a formula of a traditional Chinese medicine that is used to treat asthma patients and has been shown to have several important properties,such as antioxidant and free radical scavenging activities.The influence of an extract of Liu Wei Di Huang Wan on the labeling of blood constituents with technetium-99m was investigated.Anticoagulated blood(Wistar rats) was incubated with the extract,stannous chloride and technetium-99m,as sodium pertechnetate.Samples were centrifuged and aliquots of plasma and blood cells were separated and precipitated with trichloroacetic acid,to obtain soluble and insoluble fractions of the blood constituents.The percentage of radioactivity(%ATI) in all the fractions was determined.The analysis of the results shows that the extract at the highest concentration used(70 mg/mL) decreased significantly(P<0.05) the %ATI(from 96.48 ± 1.19 to 54.46 ± 7.38) on blood cells compartment,(from 81.11 ± 4.15 to 61.33 ± 4.74) on insoluble fractions of blood cells and(from 65.91 ± 2.44 to 13.15 ± 3.62) on insoluble fractions of plasma.In conclusion,the results suggest that the substances present on this extract can alter this labeling process,probably due to(i) redox properties(antioxidant and chelator activities) and/or(ii) specific actions in the binding sites where the 99mTc would be bound on the blood constituents.As a consequence,precaution is suggested on the interpretation of the nuclear medicine results from performed with blood constituents labeled with 99m Tc in patients that have undertaken LWDHW,although the current findings were obtained in experimental animal models.     

Molecular architecture of native HIV-1 gp120 trimers

The envelope glycoproteins (Env) of human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate virus binding to the cell surface receptor CD4 on target cells to initiate infection. Env is a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120), and forms trimers on the surface of the viral membrane. Using cryo-electron tomography combined with three-dimensional image classification and averaging, we report the three-dimensional structures of trimeric Env displayed on native HIV-1 in the unliganded state, in complex with the broadly neutralizing antibody b12 and in a ternary complex with CD4 and the 17b antibody. By fitting the known crystal structures of the monomeric gp120 core in the b12- and CD4/17b-bound conformations into the density maps derived by electron tomography, we derive molecular models for the native HIV-1 gp120 trimer in unliganded and CD4-bound states. We demonstrate that CD4 binding results in a major reorganization of the Env trimer, causing an outward rotation and displacement of each gp120 monomer. This appears to be coupled with a rearrangement of the gp41 region along the central axis of the trimer, leading to closer contact between the viral and target cell membranes. Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells.     

Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL

Autosomal recessive osteopetrosis is usually associated with normal or elevated numbers of nonfunctional osteoclasts. Here we report mutations in the gene encoding RANKL (receptor activator of nuclear factor-KB ligand) in six individuals with autosomal recessive osteopetrosis whose bone biopsy specimens lacked osteoclasts. These individuals did not show any obvious defects in immunological parameters and could not be cured by hematopoietic stem cell transplantation; however, exogenous RANKL induced formation of functional osteoclasts from their monocytes, suggesting that they could, theoretically, benefit from exogenous RANKL administration.     

Identification and characterization of new functional truncated variants of somatostatin receptor subtype 5 in rodents

Somatostatin and cortistatin exert multiple biological actions through five receptors (sst1-5); however, not all their effects can be explained by activation of sst1-5. Indeed, we recently identified novel truncated but functional human sst5-variants, present in normal and tumoral tissues. In this study, we identified and characterized three novel truncated sst5 variants in mice and one in rats displaying different numbers of transmembrane-domains [TMD; sst5TMD4, sst5TMD2, sst5TMD1 (mouse-variants) and sst5TMD1 (rat-variant)]. These sst5 variants: (1) are functional to mediate ligand-selective-induced variations in [Ca²⁺]_i and cAMP despite being truncated; (2) display preferential intracellular distribution; (3) mostly share full-length sst5 tissue distribution, but exhibit unique differences; (4) are differentially regulated by changes in hormonal/metabolic environment in a tissue- (e.g., central vs. systemic) and ligand-dependent manner. Altogether, our results demonstrate the existence of new truncated sst5-variants with unique ligand-selective signaling properties, which could contribute to further understanding the complex, distinct pathophysiological roles of somatostatin and cortistatin.     

tRNA nucleotidyltransferases: ancient catalysts with an unusual mechanism of polymerization

RNA polymerases are important enzymes involved in the realization of the genetic information encoded in the genome. Thereby, DNA sequences are used as templates to synthesize all types of RNA. Besides these classical polymerases, there exists another group of RNA polymerizing enzymes that do not depend on nucleic acid templates. Among those, tRNA nucleotidyltransferases show remarkable and unique features. These enzymes add the nucleotide triplet C–C–A to the 3′-end of tRNAs at an astonishing fidelity and are described as “CCA-adding enzymes”. During this incorporation of exactly three nucleotides, the enzymes have to switch from CTP to ATP specificity. How these tasks are fulfilled by rather simple and small enzymes without the help of a nucleic acid template is a fascinating research area. Surprising results of biochemical and structural studies allow scientists to understand at least some of the mechanistic principles of the unique polymerization mode of these highly unusual enzymes.     

The modal-Hamiltonian interpretation and the Galilean covariance of quantum mechanics

The aim of this paper is to analyze the modal-Hamiltonian interpretation of quantum mechanics in the light of the Galilean group. In particular, it is shown that the rule of definite-value assignment proposed by that interpretation has the same properties of Galilean covariance and invariance as the Schrödinger equation. Moreover, it is argued that, when the Schrödinger equation is invariant, the rule can be reformulated in an explicitly invariant form in terms of the Casimir operators of the Galilean group. Finally, the possibility of extrapolating the rule to quantum field theory is considered.     

Following the signal sequence from ribosomal tunnel exit to signal recognition particle

Membrane and secretory proteins can be co-translationally inserted into or translocated across the membrane. This process is dependent on signal sequence recognition on the ribosome by the signal recognition particle (SRP), which results in targeting of the ribosome-nascent-chain complex to the protein-conducting channel at the membrane. Here we present an ensemble of structures at subnanometre resolution, revealing the signal sequence both at the ribosomal tunnel exit and in the bacterial and eukaryotic ribosome-SRP complexes. Molecular details of signal sequence interaction in both prokaryotic and eukaryotic complexes were obtained by fitting high-resolution molecular models. The signal sequence is presented at the ribosomal tunnel exit in an exposed position ready for accommodation in the hydrophobic groove of the rearranged SRP54 M domain. Upon ribosome binding, the SRP54 NG domain also undergoes a conformational rearrangement, priming it for the subsequent docking reaction with the NG domain of the SRP receptor. These findings provide the structural basis for improving our understanding of the early steps of co-translational protein sorting.