Spatial and topological organization of DNA chains induced by gene co-localization

Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In particular, highly transcribed genes, RNA polymerases and transcription factors gather into discrete spatial foci called transcription factories. However, the mechanisms underlying the formation of these foci and the resulting topological order of the chromosome remain to be elucidated. Here we consider a thermodynamic framework based on a worm-like chain model of chromosomes where sparse designated sites along the DNA are able to interact whenever they are spatially close-by. This is motivated by recurrent evidence that there exists physical interactions between genes that operate together. Three important results come out of this simple framework. First, the resulting formation of transcription foci can be viewed as a micro-phase separation of the interacting sites from the rest of the DNA. In this respect, a thermodynamic analysis suggests transcription factors to be appropriate candidates for mediating the physical interactions between genes. Next, numerical simulations of the polymer reveal a rich variety of phases that are associated with different topological orderings, each providing a way to increase the local concentrations of the interacting sites. Finally, the numerical results show that both one-dimensional clustering and periodic location of the binding sites along the DNA, which have been observed in several organisms, make the spatial co-localization of multiple families of genes particularly efficient.Comment: Figures and Supplementary Material freely available on http://dx.doi.org/10.1371/journal.pcbi.100067

Seniority and Job Stability: A Quantile Regression Approach Using Matched Employer-Employee Data

Job mobility and employment durations can be explained by different theoretical approaches, such as job matching or human capital theory or dual labor market approaches. These models may, however, apply to different degrees at different durations in the employment spell. Standard empirical techniques, such as hazard rate analysis, cannot deal with this problem. In this paper, we apply censored quantile regression techniques to estimate employment durations of male workers in Germany. Our results give some support to the job matching model: individuals with a high risk of being bad matches exhibit higher exit rates initially, but the effect fades out over time. By contrast, the influence of human capital variables such as education and further training decreases with employment duration, which is inconsistent with the notion of increasing match-specific rents due to human capital accumulation. The results also suggest that the effects of certain labor market institutions, such as works councils, differ markedly between short-term and long-term employment, supporting the view that institutions give rise to dual labor markets

The Aims of Lifelong Learning: Age-Related Effects of Training on Wages and Job Security

This study analyses the effects of training participation on wages and perceived job security for employees of different ages. Based on data from the German Socio-Economic Panel, results indicate that only younger workers benefit from training by an increase in wages, whereas older employees' worries about losing their job are reduced. This observation can also be explained by the fact that goals of training courses are related to the age of participants. Moreover, I differentiate between workers who permanently and only occasionally participate in training. The results indicate that there seem to be decreasing marginal returns to training with respect to job security

Drug-target network in myocardial infarction reveals multiple side effects of unrelated drugs

The systems-level characterization of drug-target associations in myocardial infarction (MI) has not been reported to date. We report a computational approach that combines different sources of drug and protein interaction information to assemble the myocardial infarction drug-target interactome network (My-DTome). My-DTome comprises approved and other drugs interlinked in a single, highly-connected network with modular organization. We show that approved and other drugs may both be highly connected and represent network bottlenecks. This highlights influential roles for such drugs on seemingly unrelated targets and pathways via direct and indirect interactions. My-DTome modules are associated with relevant molecular processes and pathways. We find evidence that these modules may be regulated by microRNAs with potential therapeutic roles in MI. Different drugs can jointly impact a module. We provide systemic insights into cardiovascular effects of non-cardiovascular drugs. My-DTome provides the basis for an alternative approach to investigate new targets and multidrug treatment in MI

Salve Regina Arboretum Ten Year Plan to Reach Level III Accreditation

The Salve Regina University Arboretum, located in Newport, Rhode Island is currently registered as a Level II arboretum and is intertwined with the city of Newport Arboretum. The university now has intentions to reach Level III status, as part of a ten-year plan. This plan was developed by the students of the Spring 2018 BIO 255: Conservation Biology course, instructed by Dr. Jameson Chace, Associate Professor of biology at Salve Regina University. As part of a curriculum geared towards civic engagement, the class focused on creating and optimizing strategies that can be applied to the ten-year plan. These strategies were applied to the plan categorically: a team to inventory the current tree collection; a team to develop formal educational programming; a team for informal educational programming; a team to establish goals for conservation initiative related to the arboretum; a team dedicated to research related to arboreta; and a team to develop a list of species of special interest to add to the arboretum in the coming years. In the following document, each team’s strategies for the ten-year plan are outlined. Each of the components of this plan incorporate means to fulfill the conditions to meet Level III arboretum status so that the arboretum can apply for official registration. The aforementioned teams were tasked with designing a foundation on which to work up from. This includes formal educational programming to be applied to classroom settings and informal educational programming which can be applied to community outreach-based settings. The teams that worked to strengthen the arboretum’s mission of conservation focused on researching trees that can fit into the current landscape while providing some sort of benefit to the surrounding flora/fauna. Further, many of the species of interest, such as the chestnut, hold historical value to the greater Rhode Island region. In all, the Salve Regina Arboretum must achieve a total of 500 unique species of trees and woody plants as part of its efforts to apply for Level III status. In addition to the programming and research performed so far by the student teams, the arboretum must also hire a curator to manage the programming and to oversee the arboretum as a whole. Additionally, the arboretum must continue to actively collaborate with other arboreta and should encourage scientific research. It is important to recognize that the Salve Regina University Arboretum has already been utilized in the field of microbiology and has gained some attention at the university as a resource for further research and investigation. This ten year plan, along with resources within in it, is designed to provide a list of potential guidelines and ideas that can be applied for the arboretum’s benefit and growth. The Salve Regina University arboretum is a continually growing and developing part of the greater Newport, Rhode Island community, and will continue to strengthen its mission and that of the university which oversees its success.https://digitalcommons.salve.edu/bio255_arboretum/1000/thumbnail.jp

A Motor Function for the DEAD-Box RNA Helicase, Gemin3, in Drosophila

The survival motor neuron (SMN) protein, the determining factor for spinal muscular atrophy (SMA), is complexed with a group of proteins in human cells. Gemin3 is the only RNA helicase in the SMN complex. Here, we report the identification of Drosophila melanogaster Gemin3 and investigate its function in vivo. Like in vertebrates, Gemin3 physically interacts with SMN in Drosophila. Loss of function of gemin3 results in lethality at larval and/or prepupal stages. Before they die, gemin3 mutant larvae exhibit declined mobility and expanded neuromuscular junctions. Expression of a dominant-negative transgene and knockdown of Gemin3 in mesoderm cause lethality. A less severe Gemin3 disruption in developing muscles leads to flightless adults and flight muscle degeneration. Our findings suggest that Drosophila Gemin3 is required for larval development and motor function

Determinants of Initiation Codon Selection during Translation in Mammalian Cells

Factors affecting translation of mRNA contribute to the complexity of eukaryotic proteomes. In some cases, translation of a particular mRNA can generate multiple proteins. However, the factors that determine whether ribosomes initiate translation from the first AUG codon in the transcript, from a downstream codon, or from multiple sites are not completely understood. Various mRNA properties, including AUG codon-accessibility and 5′ leader length have been proposed as potential determinants that affect where ribosomes initiate translation. To explore this issue, we performed studies using synthetic mRNAs with two in-frame AUG codons−both in excellent context. Open reading frames initiating at AUG1 and AUG2 encode large and small isoforms of a reporter protein, respectively. Translation of such an mRNA in COS-7 cells was shown to be 5′ cap-dependent and to occur efficiently from both AUG codons. AUG codon-accessibility was modified by using two different elements: an antisense locked nucleic acid oligonucleotide and an exon-junction complex. When either element was used to mask AUG1, the ratio of the proteins synthesized changed, favoring the smaller (AUG2-initiated) protein. In addition, we observed that increased leader length by itself changed the ratio of the proteins and favored initiation at AUG1. These observations demonstrate that initiation codon selection is affected by various factors, including AUG codon-accessibility and 5′ leader length, and is not necessarily determined by the order of AUG codons (5′→3′). The modulation of AUG codon accessibility may provide a powerful means of translation regulation in eukaryotic cells