MAP Kinase‐Dependent RUNX2 Phosphorylation Is Necessary for Epigenetic Modification of Chromatin During Osteoblast Differentiation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137207/1/jcp25517.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137207/2/jcp25517_am.pd

Travelling wave solutions of the perturbed mKdV equation that represent traffic congestion

A well-known optimal velocity (OV) model describes vehicle motion along a single lane road, which reduces to a perturbed modified Korteweg-de Vries (mKdV) equation within the unstable regime. Steady travelling wave solutions to this equation are then derived with a multi-scale perturbation technique, where the travelling wave propagation coordinate depends upon slow and fast variables. The leading order solution in the hierarchy is then written in terms of these multi-scaled variables. At the following order, a system of differential equations is highlighted that govern the slowly evolving properties of the leading solution. Next, it is shown that the critical points of this system signify travelling waves without slow variation. As a result, a family of steady waves with constant amplitude and period are identified. When periodic boundary conditions are satisfied, these solutions' parameters, including the wave speed, are associated with the driver's sensitivity, $\hat{a}$, which appears in the OV model. For some given $\hat{a}$, solutions of both an upward and downward form exist, with the downward type corresponding to traffic congestion. Numerical simulations are used to validate the asymptotic analysis and also to examine the long-time behaviour of our solutions

Abundant Human DNA Contamination Identified in Non-Primate Genome Databases

During routine screens of the NCBI databases using human repetitive elements we discovered an unlikely level of nucleotide identity across a broad range of phyla. To ascertain whether databases containing DNA sequences, genome assemblies and trace archive reads were contaminated with human sequences, we performed an in depth search for sequences of human origin in non-human species. Using a primate specific SINE, AluY, we screened 2,749 non-primate public databases from NCBI, Ensembl, JGI, and UCSC and have found 492 to be contaminated with human sequence. These represent species ranging from bacteria (B. cereus) to plants (Z. mays) to fish (D. rerio) with examples found from most phyla. The identification of such extensive contamination of human sequence across databases and sequence types warrants caution among the sequencing community in future sequencing efforts, such as human re-sequencing. We discuss issues this may raise as well as present data that gives insight as to how this may be occurring

Targeting uracil-DNA glycosylases for therapeutic outcomes using insights from virus evolution

Ung-type uracil-DNA glycosylases are frontline defenders of DNA sequence fidelity in bacteria, plants, and animals; Ungs also directly assist both innate and humoral immunity. Critically important in viral pathogenesis, whether acting for or against viral DNA persistence, Ungs also have therapeutic relevance to cancer, microbial, and parasitic diseases. Ung catalytic specificity is uniquely conserved, yet selective antiviral drugging of the Ung catalytic pocket is tractable. However, more promising precision therapy approaches present themselves via insights from viral strategies, including sequestration or adaptation of Ung for non-canonical roles. A universal Ung inhibition mechanism, converged upon by unrelated viruses, could also inform design of compounds to inhibit specific distinct Ungs. Extrapolating current developments, the character of such novel chemical entities is proposed

Sudestada1, a Drosophila ribosomal prolyl-hydroxylase required for mRNA translation, cell homeostasis, and organ growth

Genome sequences predict the presence of many 2-oxoglutarate (2OG)-dependent oxygenases of unknown biochemical and biological functions in Drosophila. Ribosomal protein hydroxylation is emerging as an important 2OG oxygenase catalyzed pathway, but its biological functions are unclear. We report investigations on the function of Sudestada1 (Sud1), a Drosophila ribosomal oxygenase. As with its human and yeast homologs, OGFOD1 and Tpa1p, respectively, we identified Sud1 to catalyze prolyl-hydroxylation of the small ribosomal subunit protein RPS23. Like OGFOD1, Sud1 catalyzes a single prolyl-hydroxylation of RPS23 in contrast to yeast Tpa1p, where Pro-64 dihydroxylation is observed. RNAi-mediated Sud1 knockdown hinders normal growth in different Drosophila tissues. Growth impairment originates from both reduction of cell size and diminution of the number of cells and correlates with impaired translation efficiency and activation of the unfolded protein response in the endoplasmic reticulum. This is accompanied by phosphorylation of eIF2α and concomitant formation of stress granules, as well as promotion of autophagy and apoptosis. These observations, together with those on enzyme homologs described in the companion articles, reveal conserved biochemical and biological roles for a widely distributed ribosomal oxygenase.Fil: Katz, Maximiliano Javier. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Acevedo, Julieta Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Loenarz, Christoph. University of Oxford; Reino UnidoFil: Galagovsky, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Liu Yi, Phebee. University Of Oxford; Reino UnidoFil: Pérez, Marcelo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Thalhammer, Armin. University of Oxford; Reino UnidoFil: Sekirnik, Rok. University Of Oxford; Reino UnidoFil: Ge, Wei. University of Oxford; Reino UnidoFil: Melani, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Thomas, Maria Gabriela. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Simonetta, Sergio Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Boccaccio, Graciela Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Schofield, Christoper J. University of Oxford; Reino UnidoFil: Cockman, Matthew E. University of Oxford; Reino UnidoFil: Ratcliffe, Peter J. University of Oxford; Reino UnidoFil: Wappner, Pablo. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentin

Neuron–astrocyte interactions in the medial nucleus of the trapezoid body

The calyx of Held (CoH) synapse serves as a model system to analyze basic mechanisms of synaptic transmission. Astrocyte processes are part of the synaptic structure and contact both pre- and postsynaptic membranes. In the medial nucleus of the trapezoid body (MNTB), midline stimulation evoked a current response that was not mediated by glutamate receptors or glutamate uptake, despite the fact that astrocytes express functional receptors and transporters. However, astrocytes showed spontaneous Ca2+ responses and neuronal slow inward currents (nSICs) were recorded in the postsynaptic principal neurons (PPNs) of the MNTB. These currents were correlated with astrocytic Ca2+ activity because dialysis of astrocytes with BAPTA abolished nSICs. Moreover, the frequency of these currents was increased when Ca2+ responses in astrocytes were elicited. NMDA antagonists selectively blocked nSICs while D-serine degradation significantly reduced NMDA-mediated currents. In contrast to previous studies in the hippocampus, these NMDA-mediated currents were rarely synchronized

Estimation of changes in the force of infection for intestinal and urogenital schistosomiasis in countries with Schistosomiasis Control Initiative-assisted programmes

The last decade has seen an expansion of national schistosomiasis control programmes in Africa based on large-scale preventative chemotherapy. In many areas this has resulted in considerable reductions in infection and morbidity levels in treated individuals. In this paper, we quantify changes in the force of infection (FOI), defined here as the per (human) host parasite establishment rate, to ascertain the impact on transmission of some of these programmes under the umbrella of the Schistosomiasis Control Initiative (SCI)

Endometriosis and Headache

Headache and endometriosis show some similarities in their clinical and epidemiological features that are probably due to the influence of female sexual hormones on both disorders. Epidemiological studies indicate that they are comorbid disorders. However, the nature of the comorbidity is not known with certainty, but a likely explanation may be common susceptibility genes. Another possibility is that, because they both are related to pain, increased pain sensitivity induced by one of the disorders may lead to a higher likelihood of developing the other, possibly mediated by nitrogen oxide or prostaglandins. A common link to the widespread use of estroprogestins may seem less probable. For physicians dealing with women with either of these disorders, awareness of the comorbidity may be helpful in the treatment of the patient

Construction and demolition waste - a shift toward Lean Construction and Building Information Model

Waste in the construction industry is a devastating dilemma, especially that construction and demolition activities are considered as the highest waste generator globally. Countries have developed regulations: policy-makers and professional associations have provided norms and policies to manage C&D waste. Previous studies, however, have revealed insufficiencies in the current regulations and norms in incentivizing the industry practices toward waste prevention, since its culture is characterized by the gap in technological use, insufficient knowledge, poor planning, and poor information flow. This research provides a literature review on the current research findings and trends in managing C&D waste. Then based on design theory and theory of production, an exploratory research consisting of BIM and Lean construction concepts is provided. Lean can maximize the value of construction by addressing waste within portfolios, projects, and operations; BIM offers an enhanced collaborative platform with improved design practice and information management throughout buildings’ life cycle. The proposed conceptual framework enables economic, environmental, and social benefits to allow practitioners collaborate, analyze, and minimize construction waste throughout buildings’ life cycle.(undefined