Boolean network model predicts cell cycle sequence of fission yeast

A Boolean network model of the cell-cycle regulatory network of fission yeast (Schizosaccharomyces Pombe) is constructed solely on the basis of the known biochemical interaction topology. Simulating the model in the computer, faithfully reproduces the known sequence of regulatory activity patterns along the cell cycle of the living cell. Contrary to existing differential equation models, no parameters enter the model except the structure of the regulatory circuitry. The dynamical properties of the model indicate that the biological dynamical sequence is robustly implemented in the regulatory network, with the biological stationary state G1 corresponding to the dominant attractor in state space, and with the biological regulatory sequence being a strongly attractive trajectory. Comparing the fission yeast cell-cycle model to a similar model of the corresponding network in S. cerevisiae, a remarkable difference in circuitry, as well as dynamics is observed. While the latter operates in a strongly damped mode, driven by external excitation, the S. pombe network represents an auto-excited system with external damping.Comment: 10 pages, 3 figure

Restrictive ID policies: implications for health equity

We wish to thank Synod Community Services for their critical work to develop, support, and implement a local government-issued ID in Washtenaw County, MI. We also thank Yousef Rabhi of the Michigan House of Representatives and Janelle Fa'aola of the Washtenaw ID Task Force, Lawrence Kestenbaum of the Washtenaw County Clerk's Office, Sherriff Jerry Clayton of the Washtenaw County Sherriff's Office, and the Washtenaw ID Task Force for their tireless commitment to developing and supporting the successful implementation of the Washtenaw ID. Additionally, we thank Vicenta Vargas and Skye Hillier for their contributions to the Washtenaw ID evaluation. We thank the Curtis Center for Research and Evaluation at the University of Michigan School of Social Work, the National Center for Institutional Diversity at the University of Michigan, and the University of California-Irvine Department of Chicano/Latino Studies and Program in Public Health for their support of the Washtenaw ID community-academic research partnership. Finally, we thank the reviewers for their helpful comments on earlier drafts of this manuscript. (Curtis Center for Research and Evaluation at the University of Michigan School of Social Work; National Center for Institutional Diversity at the University of Michigan; University of California-Irvine Department of Chicano/Latino Studies; Program in Public Health)https://link.springer.com/content/pdf/10.1007/s10903-017-0579-3.pdfPublished versio

Association of symptoms of insomnia and sleep parameters among kidney transplant recipients

Objective: Insomnia complaints are frequent among kidney transplant (kTx) recipients and are associated with fatigue, depression, lower quality of life and increased morbidity. However, it is not known if subjective insomnia symptoms are associated with objective parameters of sleep architecture. Thus, we analyze the association between sleep macrostructure and EEG activity versus insomnia symptoms among kTx recipients. Methods: Participants (n1 = 100) were selected from prevalent adult transplant recipients (n0 = 1214) followed at a single institution. Insomnia symptoms were assessed by the Athens Insomnia Scale (AIS) and standard overnight polysomnography was performed. In a subgroup of patients (n2 = 56) sleep microstructure was also analyzed with power spectral analysis. Results: In univariable analysis AIS score was not associated with sleep macrostructure parameters (sleep latency, total sleep time, slow wave sleep, wake after sleep onset), nor with NREM and REM beta or delta activity in sleep microstructure. In multivariable analysis after controlling for covariables AIS score was independently associated with the proportion of slow wave sleep (β = 0.263; CI: 0.026–0.500) and REM beta activity (β = 0.323; CI = 0.041–0.606) (p < 0.05 for both associations). Conclusions: Among kTx recipients the severity of insomnia symptoms is independently associated with higher proportion of slow wave sleep and increased beta activity during REM sleep but not with other parameters sleep architecture. The results suggest a potential compensatory sleep protective mechanism and a sign of REM sleep instability associated with insomnia symptoms among this population

The personal experience of parenting a child with Juvenile Huntington’s Disease: perceptions across Europe

The study reported here presents a detailed description of what it is like to parent a child with juvenile Huntington’s disease in families across four European countries. Its primary aim was to develop and extend findings from a previous UK study. The study recruited parents from four European countries: Holland, Italy, Poland and Sweden,. A secondary aim was to see the extent to which the findings from the UK study were repeated across Europe and the degree of commonality or divergence across the different countries. Fourteen parents who were the primary caregiver took part in a semistructured interview. These were analyzed using an established qualitative methodology, interpretative phenomenological analysis. Five analytic themes were derived from the analysis: the early signs of something wrong; parental understanding of juvenile Huntington’s disease; living with the disease; other people’s knowledge and understanding; and need for support. These are discussed in light of the considerable convergence between the experiences of families in the United Kingdom and elsewhere in Europe

Synthesis, Structural and Magnetic Characterization of a New Copper(II)-Nitronyl Nitroxide Radical Complex

In this work we describe the structure and the magnetic properties of a new copper(II)-NIT complex, where NIT stands for nitronyl nitroxide radical. This was achieved using (NBu4)4[Cu2(bopba)] as a precursor (where NBu4+ is the tetrabutylammonium cation and bopba is bis-o-phenylenebis(oxamate)), whose crystal structure was resolved and its magnetics properties studied. From the reaction of this precursor with a cationic nitronyl nitroxide radical, a new compound was prepared and magnetically characterized, namely (pEtRad)4[Cu2(bopba)] (where pEtRad+ stands for the cationic para-2-(4-pyridil)-4,4,5,5-tetramethylimidazoline-1 -oxyl-3-oxide radical). The magnetic properties suggest that in this six-spin complex there is a competition between short range ferromagnetic and antiferromagnetic interactions. The ferromagnetic interaction can be explained by the orthogonality of the involved magnetic orbitals

TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy.

The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45–47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression

Quantitative antisense screening and optimization for exon 51 skipping in Duchenne muscular dystrophy

International audienceDuchenne muscular dystrophy (DMD), the most common lethal genetic disorder, is caused by mutations in the dystrophin (DMD) gene. Exon skipping is a therapeutic approach that uses antisense oligonucleotides (AOs) to modulate splicing and restore the reading frame, leading to truncated, yet functional protein expression. In 2016, the US Food and Drug Administration (FDA) conditionally approved the first phosphorodiamidate morpholino oligomer (morpholino)-based AO drug, eteplirsen, developed for DMD exon 51 skipping. Eteplirsen remains controversial with insufficient evidence of its therapeutic effect in patients. We recently developed an in silico tool to design antisense morpholino sequences for exon skipping. Here, we designed morpholino AOs targeting DMD exon 51 using the in silico tool and quantitatively evaluated the effects in immortalized DMD muscle cells in vitro. To our surprise, most of the newly designed morpholinos induced exon 51 skipping more efficiently compared with the eteplirsen sequence. The efficacy of exon 51 skipping and rescue of dystrophin protein expression were increased by up to more than 12-fold and 7-fold, respectively, compared with the eteplirsen sequence. Significant in vivo efficacy of the most effective morpholino, determined in vitro, was confirmed in mice carrying the human DMD gene. These findings underscore the importance of AO sequence optimization for exon skipping