Perspective: the size-complexity rule

It is widely accepted that bigger entities have a greater division of labor than smaller ones and this is reflected in the fact that larger multicellular organisms have a corresponding increase in the number of their cell types. This rule is examined in some detail from very small organisms to large animals, and plants, and societies. Compared to other size-related rules, the size-complexity rule is relatively rough and approximate, yet clearly it holds throughout the whole range of living organisms, as well as for societies. The relationship between size and complexity is analyzed by examining the effects of size increase and decrease: size increase requires an increase in complexity, whereas size decrease permits, and sometimes requires, a decrease in complexity. Conversely, an increase or decrease in complexity permits, but does not require changes in size. An especially compelling argument for the close relation between size and complexity can be found in size quorum sensing in very small multicellular organisms.     

Humoral immune responses to a single allele PfAMA1 vaccine in healthy malaria-naïve adults

Plasmodium falciparum: apical membrane antigen 1 (AMA1) is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. The polymorphic nature of AMA1 may compromise vaccine induced protection. The humoral response induced by two dosages (10 and 50 μg) of a single allele AMA1 antigen (FVO) formulated with Alhydrogel, Montanide ISA 720 or AS02 was investigated in 47 malaria-na?ve adult volunteers. Volunteers were vaccinated 3 times at 4 weekly intervals and serum samples obtained four weeks after the third immunization were analysed for (i) Antibody responses to various allelic variants, (ii) Domain specificity, (iii) Avidity, (iv) IgG subclass levels, by ELISA and (v) functionality of antibody responses by Growth Inhibition Assay (GIA). About half of the antibodies induced by vaccination cross reacted with heterologous AMA1 alleles. The choice of adjuvant determined the magnitude of the antibody response, but had only a marginal influence on specificity, avidity, domain recognition or subclass responses. The highest antibody responses were observed for AMA1 formulated with AS02. The Growth Inhibition Assay activity of the antibodies was proportional to the amount of antigen specific IgG and the functional capacity of the antibodies was similar for heterologous AMA1-expressing laboratory strains. Trial registration: ClinicalTrials.gov NCT00730782.     

Large isoforms of UNC-89 (obscurin) are required for muscle cell architecture and optimal calcium release in Caenorhabditis elegans

Calcium, a ubiquitous intracellular signaling molecule, controls a diverse array of cellular processes. Consequently, cells have developed strategies to modulate the shape of calcium signals in space and time. The force generating machinery in muscle is regulated by the influx and efflux of calcium ions into the muscle cytoplasm. In order for efficient and effective muscle contraction to occur, calcium needs to be rapidly, accurately and reliably regulated. The mechanisms underlying this highly regulated process are not fully understood. Here, we show that the Caenorhabditis elegans homolog of the giant muscle protein obscurin, UNC-89, is required for normal muscle cell architecture. The large immunoglobulin domain-rich isoforms of UNC-89 are critical for sarcomere and sarcoplasmic reticulum organization. Furthermore, we have found evidence that this structural organization is crucial for excitation-contraction coupling in the body wall muscle, through the coordination of calcium signaling. Thus, our data implicates UNC-89 in maintaining muscle cell architecture and that this precise organization is essential for optimal calcium mobilization and efficient and effective muscle contraction.     

Retinal stem cells: promising candidates for retina transplantation

Stem cell transplantation is widely considered as a promising therapeutic approach for photoreceptor degeneration, one of the major causes of blindness. In this review, we focus on the biology of retinal stem cells (RSCs) and progenitor cells (RPCs) isolated from fetal, postnatal, and adult animals, with emphasis on those from rodents and humans. We discuss the origin of RSCs/RPCs, the markers expressed by these cells and the conditions for the isolation, culture, and differentiation of these cells in vitro or in vivo by induction with exogenous stimulation. Commercial disclosure: none.     

Control of albumin and alpha-fetoprotein expression in rat liver and in some transplantable hepatocellular carcinomas.

Albumin and alpha-fetoprotein production by rat liver and by four selected transplantable hepatocellular carcinomas is compared to the messenger RNA present in these tissues. Albumin and alpha-fetoprotein were measured by radioimmunoassay of serum concentration, immunofluorescence, and in vitro incorporation of labeled amino acids into proteins specifically precipitated by antisera. The number of mRNA molecules per cell was calculated from the hybridization of specific cDNA probes to polysomal mRNA and by translational activity of polysomal RNA in a wheat germ system. The amount of albumin and alpha-fetoprotein produced by the different tissues is directly related to the number of functional mRNA molecules per cell for each protein.     

Histone phosphorylation during liver regeneration.

The pattern of histone phosphorylation at acid-stable, alkali-labile sites has been examined throughout the early stages of liver regeneration, namely at times of “gene activation”. Among the histones, only H1 shows an increase in phosphorylation. This increase initiates near the end of the period of chromatin template activation. Thus, there is no obvious temporal correlation between increased histone phosphorylation and increased RNA synthesis. The relative levels of phosphorylation of the various histones and the change in H1 phosphorylation observed in the liver system closely parallel the patterns exhibited by cultured animal cells during the G1 and S phases of the cycle as described by other investigators.