Novel marine alkaloids from the tunicate Eudistoma sp. are potent regulators of cellular growth and differentiation and affect cAMP-mediated processes

Six novel alkaloids that contain a fused tetracyclic pyrido[2,3,4-kl]acridine ring system were purified recently from the Red Sea purple tunicate Eudistoma sp. Evaluation of the effects of these alkaloids on cultured neuroblastoma and fibroblast cells revealed that they possess potent growth regulatory properties, and affect cell shape and adhesion. In mouse neuroblastoma cells, the Eudistoma alkaloids inhibited cell proliferation and induced a process of differentiation during which the cels flattened onto the surface, increased considerably in size, and extended long neurites. In hamster fibroblasts the alkaloids slowed down cell multiplication, and caused an exceptional cell flattening or elongation. In a virustransformed derivative of the hamster fibroblasts the alkaloids restored many aspects of normal cell growth and morphology. In addition, several of the alkaloids mimicked the effects of cAMP analogs on two well-characterized cAMP-mediated processes involved in hepatic glucose metabolism–inhibition of pyruvate kinase (PK) activity and induction of mRNA for phosphoenolpyruvate carboxykinase (PEPCK). All these effects suggest that the Eudistoma alkaloids may act on the cAMP signaling system. However, a single application of these compounds was sufficient to completely block cell multiplication and to induce and sustain differentiation and “reverse transformation”. Furthermore, these effects were not readily reversible following removal of the drugs. In contrast, a single application of agents that mimic or elevate cAMP induced a transient response that waned with time in culture, and the effects induced by constant elevation of cAMP reverse rapidly following drug removal. We propose that the Eudistoma alkaloids cause growth inhibition, differentiation, and reverse transformation by modifying the activity state of proteins that are involved in the regulation of cell shape and adhesion and serve as a target for the cAMP and/or other second messenger systems. © 1993 Wiley-Liss, Inc.     

Identification and Molecular Characterization of Homeologous Δ9-Stearoyl Acyl Carrier Protein Desaturase 3 Genes from the Allotetraploid Peanut (Arachis hypogaea)

The stearoyl–acyl carrier protein (ACP) desaturase (SAD) is a nuclear-encoded, plastid-localized soluble desaturase that catalyzes the conversion of stearoyl-ACP to oleoyl-ACP and plays a key role in the determination of the properties of the majority of cellular glycerolipids. Sad genes from a variety of plant species have been cloned and characterized. However, in peanut (Arachis hypogaea), an important edible and oilseed crop, these genes have not yet been characterized. By searching peanut expressed sequence tag (EST) and parallel sequencing (454) libraries, we have identified three members of the ahSad gene family. Among them, only one gene, ahSad3, was exclusively expressed during seed development and in a manner fully corresponding to oil accumulation. Both ahSad3 homeologous genes (ahSad3A and ahSad3B) were recovered from the allotetraploid peanut, and their mRNA expression levels were characterized. The open reading frames for ahSad3A and ahSad3B are 98% identical and consist of 1,158 bp, encoding a 386-full-amino-acid protein, with one intron in the coding sequence. Comparisons of the sequences of these two homeologous genes revealed seven single-nucleotide polymorphisms and one triplet insertion in the coding region. Southern blot analysis indicated that there are only two copies of the ahSad3 gene in the peanut genome. Homeolog-specific gene expression analysis showed that both ahSad3 homeologs are expressed in developing seeds, but gene expression is significantly biased toward the B genome. Our results point to ahSad3 as a possible target gene for manipulation of fatty acid saturation in A. hypogaea.     

Randomness in microtubule dynamics: an error that requires correction or an inherent plasticity required for normal cellular function?

Microtubules (MTs) play roles in regulating the mechanical structure and dynamics of cells. While MTs appear to be highly ordered structures, recent data suggest some randomness in their structure and dynamics. Part of this inherent randomness is attributed to errors and correction mechanisms are being investigated to overcome these ‘mistakes.’ However, this randomness may also be part of the normal intracellular function of MTs. It is possible that random events in MT structure and dynamics may contribute to their normal function and may even be part of an improved efficacy mechanism. An alternative view, wherein MT and kinetochore errors are part of required cell plasticity, is also discussed. These data may further support the concept of randomness in biological pathways as part of self‐organization or accurate and enhanced function.     

The Long-Run Socio-Economic Consequences of a Large Disaster: The 1995 Earthquake in Kobe

We quantify the ‘permanent’ socio-economic impacts of the Great Hanshin-Awaji (Kobe) earthquake in 1995 by employing a large-scale panel dataset of 1,719 cities, towns, and wards from Japan over three decades. In order to estimate the counterfactual—i.e., the Kobe economy without the earthquake—we use the synthetic control method. Three important empirical patterns emerge: First, the population size and especially the average income level in Kobe have been lower than the counterfactual level without the earthquake for over fifteen years, indicating a permanent negative effect of the earthquake. Such a negative impact can be found especially in the central areas which are closer to the epicenter. Second, the surrounding areas experienced some positive permanent impacts in spite of short-run negative effects of the earthquake. Much of this is associated with movement of people to East Kobe, and consequent movement of jobs to the metropolitan center of Osaka, that is located immediately to the East of Kobe. Third, the furthest areas in the vicinity of Kobe seem to have been insulated from the large direct and indirect impacts of the earthquake.     

Coping with Space Neophobia in Drosophila melanogaster: The Asymmetric Dynamics of Crossing a Doorway to the Untrodden

We discover and examine within a wide phylogenetic perspective spatial neophobia, avoidance of untrodden terrain, in fruit flies, in an experimental setup that reduces the gap between the field and the laboratory. In our setup, fruit flies use a natal fruit as their origin, freely exploring for days their surroundings, which consists of a mixture of trodden and untrodden terrain. The interface between trodden and untrodden is, however, reduced in our setup to a wide doorway, opened within a surrounding wall. Crossing this doorway, characterized by a sharp contrast interface between trodden and untrodden, generates a behavior whose dynamics betrays the flies'' space neophobia. The moment-by-moment dynamics of crossing is remarkably similar to that reported in mouse models of anxiety. This means that neophobic behavior is either homologous across arthropods and vertebrates or, not less interesting, convergent, whereby the same behavior is mediated in the two phyla by two completely different schemata.     

High SEPT9_i1 Protein Expression Is Associated with High-Grade Prostate Cancers

Septins are a family of GTP-binding cytoskeleton proteins expressed in many solid tumors. Septin 9 (SEPT9) in particular was found overexpressed in diverse carcinomas. Herein, we studied the expression of SEPT9 isoform 1 protein (SEPT9_i1) in human prostate cancer specimens. We utilized immunohistochemical staining to study the expression of SEPT9_i1 protein. Staining level was analyzed in association with clinical characteristics and the pathological Gleason grade and score. Fifty human prostate cancer specimens (42 primary tumors and 8 metastatic lesions) were stained by SEPT9_i1 antibody and analyzed. SEPT9_i1 protein was expressed in prostate cancer cells but absent in normal epithelial cells. The intensity of staining was correlated proportionally to pretreatment prostate-specific antigen (PSA) blood levels and Gleason score (P < 0.05). SEPT9_i1 was highly expressed in all metastatic lesions. A significant assocation between SEPT9_i1 expression and high Gleason score on multivariate linear regression analysis was found. We conclude that SEPT9_i1 is expressed in high-grade prostate tumors suggesting it has a significant role in prostate tumorigenesis and that it could serve as a molecular marker for prostate tumor progression.