The road less traveled to the spindle equator

Comment on: Cai S, et al. Nat Cell Biol 2009; 11:832-8.     

The road less traveled: Phylogenetic perspectives in primatology

Interest in phylogeny is increasing in many areas of evolutionary biology. One area of evolutionary anthropology that has not yet fully embraced this growth in phylogenetic thinking, however, is the study of primate behavior and ecology.¹ The predominant framework for behavioral studies of primates over the last three decades has been socioecological. The goals have been to identify broad correlations between species' behaviors and current environmental conditions. As such, the socioecological approach has been largely nonhistorical, taking little account of phylogeny. In contrast, phylogenetic approaches view the behavior of contemporary taxa within an explicitly historical framework. Although socioecology has proven extremely productive, there are many reasons to think that research in primatology could be profitably supplemented by a phylogenetic perspective.^2,3     

A road less traveled by: exploring a decade of Ellman chemistry

The Ellman group has been one of the most influential in the development and widespread adoption of combinatorial chemistry techniques for biomedical research. Their work has included substantial methodological development for library synthesis with a particular focus on new scaffolds rationally targeted to biomolecules of interest and biologically relevant natural products. Herein we analyze a representative set of libraries from this group with respect to their biological and biomedical relevance in comparison to existing drugs and probe compounds. This analysis reveals that the Ellman group has not only provided new methodologies to the community but also provided libraries with unique potential for further biological study.     

The road less traveled: transport of Legionella to the endoplasmic reticulum

Phagosomes containing the bacterial pathogen Legionella pneumophila are transported to the ER after macrophage internalization. To modulate phagosome transport, Legionella use a specialized secretion system that injects bacterial proteins into eukaryotic cells. This review will focus on recent studies that have identified bacterial proteins and host processes that play a concerted role in transporting Legionella to the ER.     

Cloning of non-human primates: the road "less traveled by"

Early studies on cloning of non-human primates by nuclear transfer utilized embryonic blastomeres from preimplantation embryos which resulted in the reproducible birth of live offspring. Soon after, the focus shifted to employing somatic cells as a source of donor nuclei (somatic cell nuclear transfer, SCNT). However, initial efforts were plagued with inefficient nuclear reprogramming and poor embryonic development when standard SCNT methods were utilized. Implementation of several key SCNT modifications was critical to overcome these problems. In particular, a non-invasive method of visualizing the metaphase chromosomes during enucleation was developed to preserve the reprogramming capacity of monkey oocytes. These modifications dramatically improved the efficiency of SCNT, yielding high blastocyst development in vitro. To date, SCNT has been successfully used to derive pluripotent embryonic stem cells (ESCs) from adult monkey skin fibroblasts. These remarkable advances have the potential for development of human autologous ESCs and cures for many human diseases. Reproductive cloning of nonhuman primates by SCNT has not been achieved yet. We have been able to establish several pregnancies with SCNT embryos which, so far, did not progress to term. In this review, we summarize the approaches, obstacles and accomplishments of SCNT in a non-human primate model.     

The partial retro-inverso modification: a road traveled together

In the mid-1970s, Dr. Murray Goodman was interested in a reversed peptide bond as a surrogate to understand the functional role of the amide bond in aspartame, a dipeptide sweetener. Very soon, realizing the breath and potential of this modification, Murray expanded this activity into a full program and I was fortunate to be part of it. Together we formulated new concepts such as the partially modified retro-inverso and end-group modified retro-inverso transformations, tested hypotheses, generated novel nomenclature, developed synthetic routes, characterized the preferred conformations of the unique building blocks employed in this modification, the gem-diaminoalkyl and the C2-substituted malonyl residues, and studied the biological activity of retro-inverso isomers of bioactive peptides. In the early 1980s several laboratories initiated extensive research targeted at the retro-inverso modification. The revival of this field led to new applications, new methods of synthesis, and new insights on the conformational and topological properties of the retro-inverso modification. Among the fields that embraced the retro-inverso concept were immunology as pertains to subjects such as synthetic vaccines, immunomodulators, and diagnostic tools, and drug delivery field as pertains to targeted and nontargeted cell permeation vectors loaded with bioactive cargo. Doctor Murray Goodman's sudden death leaves behind not only family, friends, and colleagues, but also an impressive record of scientific achievements among which is the revival of the modern era of the retro-inverso transformation. Murray's numerous contributions, excellent leadership, enthusiastic promotion, and outstanding teachings in this field will carry and illuminate his memory far into the future.     

The road much traveled: trafficking in the cell nucleus

Trafficking of RNA molecules and proteins within the cell nucleus is central to genome function. Recent work has revealed the nature of RNA and protein motion within the nucleus and across the nuclear membrane. These studies have given insight into how molecules find their destinations within the nucleus and have uncovered some of the structural properties of the nuclear microenvironment. Control of RNA and protein trafficking is now emerging as a physiological regulatory mechanism in gene expression and nuclear function.     

Protecting the human subjects of social science research--the role of institutional review boards

Current and proposed reforms of the regulatory schema for protecting human subjects of research have focused attention on Institutional Review Board (IRB) responsibilities. Consensus on the need for strengthening the oversight of these boards is all but certain--with the exception of research in the social and behavioral sciences, where an argument for less oversight is being made. The thesis in this article is that respecting the salient features of research in the social and behavioral sciences will ameliorate the tensions leading to this demand and offer better protection to the subjects of social and behavior studies.     

The well-worn route and the path less traveled: distinct neural bases of route following and wayfinding in humans

Finding one's way in a large-scale environment may engage different cognitive processes than following a familiar route. The neural bases of these processes were investigated using functional MRI (fMRI). Subjects found their way in one virtual-reality town and followed a well-learned route in another. In a control condition, subjects followed a visible trail. Within subjects, accurate wayfinding activated the right posterior hippocampus. Between-subjects correlations with performance showed that good navigators (i.e., accurate wayfinders) activated the anterior hippocampus during wayfinding and head of caudate during route following. These results coincide with neurophysiological evidence for distinct response (caudate) and place (hippocampal) representations supporting navigation. We argue that the type of representation used influences both performance and concomitant fMRI activation patterns.     

Mechanisms and consequences of methylating agent-induced SCEs and chromosomal aberrations: a long road traveled and still a far way to go

Since the milestone work of Evans and Scott, demonstrating the replication dependence of alkylation-induced aberrations, and Obe and Natarajan, pointing to the critical role of DNA double-strand breaks (DSBs) as the ultimate trigger of aberrations, the field has grown extensively. A notable example is the identification of DNA methylation lesions provoking chromosome breakage (clastogenic) effects, which made it possible to model clastogenic pathways evoked by genotoxins. Experiments with repair-deficient mutants and transgenic cell lines revealed both O6-methylguanine (O6MeG) and N- methylpurines as critical lesions. For S(N)2 agents such as methyl- methanesulfonate (MMS), base N-methylation lesions are most critical, likely because of the formation of apurinic sites blocking replication. For S(N)1 agents, such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), O6-methylguanine (O6MeG) plays the major role both in recombination and clastogenicity in the post-treatment cell cycle, provided the lesion is not pre-replicatively repaired by O6-methylguanine-DNA methyltransferase (MGMT). The conversion probability of O6MeG into SCEs and chromosomal aberrations is estimated to be about 30:1 and >10,000:1 respectively, indicating this mispairing pro-mutagenic lesion to be highly potent in inducing recombination giving rise to SCEs. O6MeG needs replication and mismatch repair to become converted into a critical secondary genotoxic lesion. Here it is proposed that this secondary lesion can be tolerated by a process termed recombination bypass. This process is supposed to be important in the tolerance of lesions that can not be processed by translesion synthesis accomplished by low-fidelity DNA polymerases. Recombination bypass results in SCEs and might represent an alternative pathway of tolerance of non-instructive lesions. In the case of O6MeG-derived secondary lesions, recombination bypass appears to protect against cell killing since SCEs are already induced with low, non-toxic doses of MNNG. Saturation of lesion tolerance by recombination bypass or translesion synthesis may cause block of DNA replication leading to DSBs at stalled replication forks, which result in chromatid-type aberrations. Along with this model, several putative consequences of methylation-induced aberrations will be discussed such as cell death by apoptosis as well its role in tumor promotion and progression.     

Rapid continental spread of a salt-tolerant plant along the European road network

The spread of alien species with the expansion of road networks and increasing traffic is a well-known phenomenon globally. Besides their corridor effects, road maintenance practices, such as the use of de-icing salts during winter facilitate the spread of halophyte (salt tolerant) species along roads. A good example is Plantago coronopus, a mainly coastal halophyte which has started spreading inland from the Atlantic and Mediterranean coastal habitats, recently reaching even Central European countries (e.g. Hungary). Here we studied the spread of this halophyte and tried to identify factors explaining its successful dispersion along roads, while also comparing native and non-native roadside occurrences with regard to altitude of the localities, size of roadside populations and frequency of roadside occurrences. We completed a comprehensive literature review and collected more than 200 reports of occurrence from roadsides spanning a total of 38 years. During systematic sampling the frequency of the species along roads was significantly higher in the Mediterranean (native area), than along Hungarian (non-native area) roads, however the average number of individuals at the sampling localities were very similar, and no significant difference could be detected. Using a germination experiment, we demonstrate that although the species is able to germinate even at high salt concentrations, salt is not required for germination. Indeed salt significantly decreases germination probability of the seeds. The successful spread of the species could most likely be explained by its remarkably high seed production, or some special characteristics (e.g. seed dimorphism) and its ability to adapt to a wide range of environmental conditions. Considering the recent and rapid eastward spread of P. coronopus, occurrences in other countries where it has not been reported yet can be predicted in coming years.

     

Eicosapentaenoic acid in serum phospholipids relates to a less atherogenic lipoprotein profile in subjects with familial hypercholesterolemia

Familial hypercholesterolemia (FH) carries an increased vascular risk due to lifelong elevation of the number of circulating low-density lipoprotein (LDL) particles, but also to alterations in triglyceride and high-density lipoprotein (HDL) metabolism. Supplementation with eicosapentaenoic (EPA) or docosahexaenoic (DHA) acids reduced LDL particle number and/or increased LDL size in different populations, but studies in FH are scarce. We investigated cross-sectionally whether intake of EPA and DHA in the usual diet is associated with a less atherogenic lipoprotein profile in subjects with FH (n=215). Lipoprotein particle number and size distributions were assessed with nuclear magnetic resonance spectroscopy. EPA and DHA proportions in serum phosphatidylcholine, a biomarker of fish intake, were determined by gas chromatography. After adjusting for cardiovascular risk factors, including fasting triglycerides, serum phosphatidylcholine EPA (but not DHA) related inversely to medium VLDL, total LDL particle number and very small LDL, resulting in a net direct association with LDL size. Additionally, EPA was directly associated with concentrations of large HDL. We conclude that increased serum phosphatidylcholine EPA derived from seafood intake with the usual diet is associated with a less atherogenic lipoprotein profile in subjects with FH. Increased fish intake and/or EPA supplements might contribute to reduce the residual risk of statin-treated FH subjects.     

Biologic effect of a hybrid preparation of human chorionic gonadotropin in human subjects

Alpha and beta-hCG subunits were recombined generating a hybrid hCG preparation (AB1ER-CR-2XY) which met the required specifications of a pharmaceutical product. The biologic activity contained in each vial of AB1ER-CR-2XY was equivalent to 10 000IU of hCG-IS. This preparation was given as a single dose of 10 000IU by the i.m. route to four female subjects presenting unexplained infertility. The hCG hybrid was demonstrated to effect gonadal stimulation in humans.     

Effects of road-traffic pollutants (lead and cadmium) on tree fine-roots along a motor road

The aim of this investigation was to study the effects of lead and cadmium pollutants from road traffic on fine roots and mycorrhiza and their accumulation in soil. The effects of salt and phosphorus, calcium and pH were furthermore included in the study. Soil sampling was carried out in a Norway spruce (Picea abies (L.) Karsten stand along the European road E18 in the neighbourhood of Västerås. Cylindrical soil samples were taken along two parallel lines at a distance of 20 and 200 m from the about 10 m open area on both sides of the road. There were more root tips per soil core in the FH-horizon 200 m from the road than near the road. The amount of fine roots (dry weight and length) was furthermore higher in the FH-layer in the forest than adjacent to the road. The estimated pH was higher in the FH- and mineral soil horizon near the road than in the forest. The lead concentration was highest in the FH-layer near the road, in spite of the high pH and calcium concentration in the soil. The lead and cadmium concentrations in dead fine-roots were higher close to the road than in the forest. In relation to lead the related cadmium concentration in the soil was very low.