Comparing prediction efficiency in the BTW and Manna sandpiles.

The state-of-the-art in the theory of self-organized criticality reveals that a certain inactivity precedes extreme events, which are located on the tail of the event probability distribution with respect to their sizes. The existence of the inactivity allows for the prediction of these events in advance. In this work, we explore the predictability of the Bak-Tang-Wiesenfeld (BTW) and Manna models on the square lattice as a function of the lattice length.

Soluble Fluorinated Cardo Copolyimide as an Effective Additive to Photopolymerizable Compositions Based on Di(meth)acrylates: Application for Highly Thermostable Primary Protective Coating of Silica Optical Fiber.

The development of photocurable compositions is in high demand for the manufacture of functional materials for electronics, optics, medicine, energy, etc. The properties of the final photo-cured material are primarily determined by the initial mixture, which needs to be tuned for each application. In this study we propose to use simple systems based on di(meth)acrylate, polyimide and photoinitiator for the preparation of new photo-curable compositions.

Genetic confounds of transgenerational epigenetic inheritance in mice.

Transgenerational epigenetic inheritance in mammals remains a controversial phenomenon. A recent study by Takahashi et al. provides evidence for this mode of inheritance in mice by using a CRISPR/Cas9-based epigenetic editing technique to modify DNA methylation levels at specific promoters and then demonstrating the inheritance of the gain in methylation in offspring.

Methyl-CpG binding domain 2 (Mbd2) is an epigenetic regulator of autism-risk genes and cognition.

The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment.

Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance.

As advances in genome engineering inch the technology towards wider clinical use-slowed by technical and ethical hurdles-a newer offshoot, termed "epigenome engineering", offers the ability to correct disease-causing changes in the DNA without changing its sequence and, thus, without some of the unfavorable correlates of doing so. In this review, we note some of the shortcomings of epigenetic editing technology-specifically the risks involved in the introduction of epigenetic enzymes-and highlight an alternative epigenetic editing strategy using physical occlusion to modify epigenetic marks at target sites without a requirement for any epigenetic enzyme. This may prove to be a safer alternative for more specific epigenetic editing.

The PROTECTOR strategy employs dCas orthologs to sterically shield off-target sites from CRISPR/Cas activity.

Off-target mutagenesis of CRISPR/Cas systems must be solved to facilitate safe gene therapy. Here, we report a novel approach, termed "PROTECTOR", to shield known off-target sites by directing the binding of an orthologous nuclease-dead Cas protein to the off-target site to sterically interfere with Cas activity. We show that this method reduces off-target mutation rates of two well-studied guide RNAs without compromising on-target activity and that it can be used in combination with high-fidelity Cas enzymes to further reduce off-target editing.

Enzyme-free targeted DNA demethylation using CRISPR-dCas9-based steric hindrance to identify DNA methylation marks causal to altered gene expression.

DNA methylation involves the enzymatic addition of a methyl group primarily to cytosine residues in DNA. This protocol describes how to produce complete and minimally confounded DNA demethylation of specific sites in the genome of cultured cells by clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9 and without the involvement of an epigenetic-modifying enzyme, the purpose of which is the evaluation of the functional (i.e.

Unraveling the functional role of DNA demethylation at specific promoters by targeted steric blockage of DNA methyltransferase with CRISPR/dCas9.

Despite four decades of research to support the association between DNA methylation and gene expression, the causality of this relationship remains unresolved. Here, we reaffirm that experimental confounds preclude resolution of this question with existing strategies, including recently developed CRISPR/dCas9 and TET-based epigenetic editors. Instead, we demonstrate a highly effective method using only nuclease-dead Cas9 and guide RNA to physically block DNA methylation at specific targets in the absence of a confounding flexibly-tethered enzyme, thereby enabling the examination of the role of DNA demethylation per se in living cells, with no evidence of off-target activity.

Reduction of DNMT3a and RORA in the nucleus accumbens plays a causal role in post-traumatic stress disorder-like behavior: reversal by combinatorial epigenetic therapy.

Post-traumatic stress disorder (PTSD) is an incapacitating trauma-related disorder, with no reliable therapy. Although PTSD has been associated with epigenetic alterations in peripheral white blood cells, it is unknown where such changes occur in the brain, and whether they play a causal role in PTSD. Using an animal PTSD model, we show distinct DNA methylation profiles of PTSD susceptibility in the nucleus accumbens (NAc).

Uncommon side effects of common drugs in patients with familial dysautonomia.

Purpose: Patients with the autosomal recessive disorder of familial dysautonomia typically exhibit exacerbated adverse side effects to many common drugs. We aimed to catalog these adverse effects - with a focus on common drugs that are frequently administered to FD patients and compare their incidences to those within the general population.

Methods: We used data of 595 FD patients from an international database with information on drugs received and adverse effects.

Transcriptome Sequencing Reveals Candidate NF-κB Target Genes Involved in Repeated Cocaine Administration.

Background: Drug-induced alterations in gene expression play an important role in the development of addictive behavior. Numerous transcription factors have been implicated in mediating the gene expression changes that occur in drug addiction. Nuclear factor kappa B is an inducible transcription factor complex that is rapidly activated by diverse stimuli.

DNA methylation controls unmethylated transcription start sites in the genome in trans.

Aim: DNA methylation downregulates transcription. However, a large number of genes, which are unmethylated in the promoter region, are inactive. We tested the hypothesis that these genes are regulated by DNA methylation of upstream regulators.

Genetic Polymorphisms in the ESR1 and VDR Genes Do Not Correlate With Osteoporosis in Patients With Familial Dysautonomia.

One of the major clinical manifestations of familial dysautonomia (FD)-a rare, neurodegenerative, autosomal-recessive disorder-is a high incidence and early onset of osteoporotic bone fractures. Early diagnosis is essential to initiate preventative therapy in at-risk patients and thus improve quality of life. However, the current lack of understanding of the complex relationship between FD and osteoporosis etiology precludes early diagnosis, and as such, accurate predictors of osteoporosis development in FD patients remain to be determined.

Anthropogenic and authigenic uranium in marine sediments of the central Gulf of California adjacent to the Santa Rosalía mining region.

To investigate the causes of uranium (U) enrichment in marine sediments in the eastern sector of the Gulf of California, surface sediments and sediment cores were collected adjacent to the Santa Rosalía copper mining region in the Baja California peninsula. Three coastal sediment cores were found to display high concentrations of U (from 54.2 ± 7.

Arsenic and mercury contamination of sediments of geothermal springs, mangrove lagoon and the Santispac bight, Bahía Concepción, Baja California peninsula.

In order to find out the environmental impact on the coastal zone, the composition of sediments of the intertidal geothermal hot spring zone and adjacent area of Playa Santispac in the pristine Bahía Concepción (Baja California peninsula) was studied. High concentrations of As (13-111 mg kg⁻¹) and Hg (0.55-25.

Determination of Np-237 by radiochemical neutron activation analysis combined with extraction chromatography.

A procedure for determination of 237Np, 238Pu, 239,240Pu and 241Pu in environmental samples is described. Neptunium-237 is determined using radiochemical neutron activation analysis with pre- and post-irradiation chemistry based on solvent extraction and extraction chromatography. 238Pu, 239,240Pu is determined using alpha spectrometry and 241Pu by liquid scintillation spectrometry.