DNA glycosylases: in DNA repair and beyond

The base excision repair machinery protects DNA in cells from the damaging effects of oxidation, alkylation, and deamination; it is specialized to fix single-base damage in the form of small chemical modifications. Base modifications can be mutagenic and/or cytotoxic, depending on how they interfere with the template function of the DNA during replication and transcription. DNA glycosylases play a key role in the elimination of such DNA lesions; they recognize and excise damaged bases, thereby initiating a repair process that restores the regular DNA structure with high accuracy. All glycosylases share a common mode of action for damage recognition; they flip bases out of the DNA helix into a selective active site pocket, the architecture of which permits a sensitive detection of even minor base irregularities. Within the past few years, it has become clear that nature has exploited this ability to read the chemical structure of DNA bases for purposes other than canonical DNA repair. DNA glycosylases have been brought into context with molecular processes relating to innate and adaptive immunity as well as to the control of DNA methylation and epigenetic stability. Here, we summarize the key structural and mechanistic features of DNA glycosylases with a special focus on the mammalian enzymes, and then review the evidence for the newly emerging biological functions beyond the protection of genome integrity

EEG Biofeedback as a Treatment for Substance Use Disorders: Review, Rating of Efficacy, and Recommendations for Further Research

Electroencephalographic (EEG) biofeedback has been employed in substance use disorder (SUD) over the last three decades. The SUD is a complex series of disorders with frequent comorbidities and EEG abnormalities of several types. EEG biofeedback has been employed in conjunction with other therapies and may be useful in enhancing certain outcomes of therapy. Based on published clinical studies and employing efficacy criteria adapted by the Association for Applied Psychophysiology and Biofeedback and the International Society for Neurofeedback and Research, alpha theta training—either alone for alcoholism or in combination with beta training for stimulant and mixed substance abuse and combined with residential treatment programs, is probably efficacious. Considerations of further research design taking these factors into account are discussed and descriptions of contemporary research are given

Investigating large-scale brain dynamics using field potential recordings: Analysis and interpretation

New technologies to record electrical activity from the brain on a massive scale offer tremendous opportunities for discovery. Electrical measurements of large-scale brain dynamics, termed field potentials, are especially important to understanding and treating the human brain. Here, our goal is to provide best practices on how field potential recordings (EEG, MEG, ECoG and LFP) can be analyzed to identify large-scale brain dynamics, and to highlight critical issues and limitations of interpretation in current work. We focus our discussion of analyses around the broad themes of activation, correlation, communication and coding. We provide best-practice recommendations for the analyses and interpretations using a forward model and an inverse model. The forward model describes how field potentials are generated by the activity of populations of neurons. The inverse model describes how to infer the activity of populations of neurons from field potential recordings. A recurring theme is the challenge of understanding how field potentials reflect neuronal population activity given the complexity of the underlying brain systems

Ionospheric convection response to slow, strong variations in a northward interplanetary magnetic field: A case study for January 14, 1988

We analyze ionospheric convection patterns over the polar regions during the passage of an interplanetary magnetic cloud on January 14, 1988, when the interplanetary magnetic field (IMF) rotated slowly in direction and had a large amplitude. Using the assimilative mapping of ionospheric electrodynamics (AMIE) procedure, we combine simultaneous observations of ionospheric drifts and magnetic perturbations from many different instruments into consistent patterns of high-latitude electrodynamics, focusing on the period of northward IMF. By combining satellite data with ground-based observations, we have generated one of the most comprehensive data sets yet assembled and used it to produce convection maps for both hemispheres. We present evidence that a lobe convection cell was embedded within normal merging convection during a period when the IMF By and Bz components were large and positive. As the IMF became predominantly northward, a strong reversed convection pattern (afternoon-to-morning potential drop of around 100 kV) appeared in the southern (summer) polar cap, while convection in the northern (winter) hemisphere became weak and disordered with a dawn-to-dusk potential drop of the order of 30 kV. These patterns persisted for about 3 hours, until the IMF rotated significantly toward the west. We interpret this behavior in terms of a recently proposed merging model for northward IMF under solstice conditions, for which lobe field lines from the hemisphere tilted toward the Sun (summer hemisphere) drape over the dayside magnetosphere, producing reverse convection in the summer hemisphere and impeding direct contact between the solar wind and field lines connected to the winter polar cap. The positive IMF Bx component present at this time could have contributed to the observed hemispheric asymmetry. Reverse convection in the summer hemisphere broke down rapidly after the ratio |By/Bz| exceeded unity, while convection in the winter hemisphere strengthened. A dominant dawn-to-dusk potential drop was established in both hemispheres when the magnitude of By exceeded that of Bz, with potential drops of the order of 100 kV, even while Bz remained northward. The later transition to southward Bz produced a gradual intensification of the convection, but a greater qualitative change occurred at the transition through |By/Bz| = 1 than at the transition through Bz = 0. The various convection patterns we derive under northward IMF conditions illustrate all possibilities previously discussed in the literature: nearly single-cell and multicell, distorted and symmetric, ordered and unordered, and sunward and antisunward