Robust synchronization of coupled circadian and cell cycle oscillators in single mammalian cells

Circadian cycles and cell cycles are two fundamental periodic processes with a period in the range of 1 day. Consequently, coupling between such cycles can lead to synchronization. Here, we estimated the mutual interactions between the two oscillators by time‐lapse imaging of single mammalian NIH3T3 fibroblasts during several days. The analysis of thousands of circadian cycles in dividing cells clearly indicated that both oscillators tick in a 1:1 mode‐locked state, with cell divisions occurring tightly 5 h before the peak in circadian Rev‐Erbα‐YFP reporter expression. In principle, such synchrony may be caused by either unidirectional or bidirectional coupling. While gating of cell division by the circadian cycle has been most studied, our data combined with stochastic modeling unambiguously show that the reverse coupling is predominant in NIH3T3 cells. Moreover, temperature, genetic, and pharmacological perturbations showed that the two interacting cellular oscillators adopt a synchronized state that is highly robust over a wide range of parameters. These findings have implications for circadian function in proliferative tissues, including epidermis, immune cells, and cancer.     

Sandbox University: Estimating Influence of Institutional Action

The approach presented in this article represents a generalizable and adaptable methodology for identifying complex interactions in educational systems and for investigating how manipulation of these systems may affect educational outcomes of interest. Multilayer Minimum Spanning Tree and Monte-Carlo methods are used. A virtual Sandbox University is created in order to facilitate effective identification of successful and stable initiatives within higher education, which can affect students'' credits and student retention – something that has been lacking up until now. The results highlight the importance of teacher feedback and teacher-student rapport, which is congruent with current educational findings, illustrating the methodology''s potential to provide a new basis for further empirical studies of issues in higher education from a complex systems perspective.     

Persistent measles virus infection of a clonal line of neuroblastoma: Effect on neural differentiation

Murine neuroblastoma cells, chronically infected with measles virus were examined for changes in neural-specific function and structure as well as cellular growth and macromolecular synthesis. When exposed to neural differentiation-inducing culture conditions, neurite formation and acetylcholinesterase activity are significantly increased in control cultures but not in persistently infected cells. Infected cultures manifest a more rapid doubling time, but depressed RNA and protein synthesis at saturation densities. Higher concentrations of papavarine, a cyclic 3′–5′ AMP phosphodiesterase inhibitor, result in selective death of persistently infected cells.     

Molecular phylogenetic analysis places Percolomonas cosmopolitus within Heterolobosea: evolutionary implications

Percolomonas cosmopolitus is a common free-living flagellate of uncertain phylogenetic position that was placed within the Heterolobosea on the basis of ultrastructure studies. To test the relationship between Percolomonas and Heterolobosea, we analysed the primary structure of the actin and small-subunit ribosomal RNA (SSU rRNA) genes of P. cosmopolitus as well as the predicted secondary structure of the SSU rRNA. Percolomonas shares common secondary structure patterns of the SSU rRNA with heterolobosean taxa, which, together with the results of actin gene analysis, confirms that it is closely related to Heterolobosea. Phylogenetic reconstructions based on the sequences of the SSU rRNA gene suggest Percolomonas belongs to the family Vahlkampfiidae. The first Bayesian analysis of a large taxon sampling of heterolobosean SSU rRNA genes clarifies the phylogenetic relationships within this group.     

Experimental allergic encephalomyelitis in the guinea pig: Variation in peripheral blood lymphocyte responsiveness to myelin basic protein during disease development

Peripheral blood lymphocytes (PBL) from guinea pigs with experimental allergic encephalomyelitis (EAE) induced by sensitization with bovine whole white matter, proliferated in vitro upon exposure to bovine myelin basic protein (B-MBP). The degree of the response increased with clinical severity. PBL from EAE-sensitized guinea pigs which failed to develop clinical disease did not respond to B-MBP. PBL from complete Freund's adjuvant-sensitized and nonsensitized normal guinea pigs were not responsive to B-MBP. EAE-sensitized animals displaying clinical signs of disease showed concanavalin A (Con A) responsiveness which paralleled that of B-MBP. Animals that did not develop EAE demonstrated Con A responses similar to those of control guinea pigs. Thus, in this acute autoimmune demyelinating condition, PBL responsiveness to B-MBP might provide a monitor of disease development.