DNA methylation acts as an epigenetic modification in vertebrate DNA. Recently it has become clear that the DNA and histone lysine methylation systems are highly interrelated and rely mechanistically ...on each other for normal chromatin function in vivo. Here we examine some of the functional links between these systems, with a particular focus on several recent discoveries suggesting how lysine methylation may help to target DNA methylation during development, and vice versa. In addition, the emerging role of non-methylated DNA found in CpG islands in defining histone lysine methylation profiles at gene regulatory elements will be discussed in the context of gene regulation. This article is part of a Special Issue entitled: Methylation: A Multifaceted Modification — looking at transcription and beyond.
Display omitted
•There is an emerging realisation that DNA and histone lysine methylation in mammals are highly interrelated.•Targeting of DNA methylation is mechanistically linked to H3K9 methylation.•Uhrf1 acts as a link between H3K9 methylation and maintenance methylation during DNA replication.•Targeting of Dnmt3a/b is influenced by H3K4 and H3K36 methylation.•Non-methylated DNA at CpG islands influences histone methylation through ZF-CxxC proteins.
The Dynamic-Processing Model of Working Memory Rose, Nathan S.
Current directions in psychological science : a journal of the American Psychological Society,
08/2020, Letnik:
29, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Recent shifts in the understanding of how the mind and brain retain information in working memory (WM) call for revision to traditional theories. Evidence of dynamic, “activity-silent,” short-term ...retention processes diverges from conventional models positing that information is always retained in WM by sustained neural activity in buffers. Such evidence comes from machine-learning methods that can decode patterns of brain activity and the simultaneous administration of transcranial magnetic stimulation (TMS) to causally manipulate brain activity in specific areas and time points. TMS can “ping” brain areas to both reactivate latent representations retained in WM and affect memory performance. On the basis of these findings, I argue for a supplement to sustained retention mechanisms. Brain-decoding methods also reveal that dynamic levels of representational codes are retained in WM, and these vary according to task context, from perceptual (sensory) codes in posterior areas to abstract, recoded representations distributed across frontoparietal regions. A dynamic-processing model of WM is advanced to account for the overall pattern of results.
Polycomb group proteins are transcriptional repressors that are essential for normal gene regulation during development. Recent studies suggest that Polycomb repressive complexes (PRCs) recognize and ...are recruited to their genomic target sites through a range of different mechanisms, which involve transcription factors, CpG island elements and non-coding RNAs. Together with the realization that the interplay between PRC1 and PRC2 is more intricate than was previously appreciated, this has increased our understanding of the vertebrate Polycomb system at the molecular level.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract
Many countries have undertaken large and high-profile payment-for-ecosystem-services (PES) programs to sustain the use of their natural resources. Nevertheless, few studies have ...comprehensively examined the impacts of existing PES programs. Grassland Ecological Compensation Policy (GECP) is one of the few pastorally focused PES programs with large investments and long duration, which aim to improve grassland quality and increase herder income. Here we present empirical evidence of the effects of GECP on grassland quality and herder income. Through a thorough and in-depth econometric analysis of remote sensing and household survey data, we find that, although GECP improves grassland quality (albeit to only a small extent) and has a large positive effect on income, it exacerbates existing income inequality among herders within their local communities. The analysis demonstrates that the program has induced herders to change their livestock production behavior. Heterogeneity analysis emphasizes the importance of making sure the programs are flexible and are adapted to local resource circumstances.
The ability to hold information in working memory is fundamental for cognition. Contrary to the long-standing view that working memory depends on sustained, elevated activity, we present evidence ...suggesting that humans can hold information in working memory via "activity-silent" synaptic mechanisms. Using multivariate pattern analyses to decode brain activity patterns, we found that the active representation of an item in working memory drops to baseline when attention shifts away. A targeted pulse of transcranial magnetic stimulation produced a brief reemergence of the item in concurrently measured brain activity. This reactivation effect occurred and influenced memory performance only when the item was potentially relevant later in the trial, which suggests that the representation is dynamic and modifiable via cognitive control. The results support a synaptic theory of working memory.
Recent studies suggest that working memory training may benefit older adults; however, findings regarding training and transfer effects are mixed. The current study aimed to investigate the effects ...of a process-based training intervention in a diverse sample of older adults and explored possible moderators of training and transfer effects. For that purpose, 80 older adults (65-95 years) were assigned either to a training group that worked on visuospatial, verbal, and executive working memory tasks for 9 sessions over 3 weeks or to a control group. Performance on trained and transfer tasks was assessed in all participants before and after the training period, as well as at a 9-month follow-up. Analyses revealed significant training effects in all 3 training tasks in trained participants relative to controls, as well as near transfer to a verbal working memory task and far transfer to a fluid intelligence task. Encouragingly, all training effects and the transfer effect to verbal working memory were stable at the 9-month follow-up session. Further analyses revealed that training gains were predicted by baseline performance in training tasks and (to a lesser degree) by age. Gains in transfer tasks were predicted by age and by the amount of improvement in the trained tasks. These findings suggest that cognitive plasticity is preserved over a large range of old age and that even a rather short training regime can lead to (partly specific) training and transfer effects. However, baseline performance, age, and training gains moderate the amount of plasticity.
Abstract
Unmanned aerial vehicles are increasingly used to study atmospheric structure and dynamics. While much emphasis has been on the development of fixed-wing unmanned aircraft for atmospheric ...investigations, the use of multirotor aircraft is relatively unexplored, especially for capturing atmospheric winds. The purpose of this article is to demonstrate the efficacy of estimating wind speed and direction with 1) a direct approach using a sonic anemometer mounted on top of a hexacopter and 2) an indirect approach using attitude data from a quadcopter. The data are collected by the multirotor aircraft hovering 10 m above ground adjacent to one or more sonic anemometers. Wind speed and direction show good agreement with sonic anemometer measurements in the initial experiments. Typical errors in wind speed and direction are smaller than 0.5
and 30°, respectively. Multirotor aircraft provide a promising alternative to traditional platforms for vertical profiling in the atmospheric boundary layer, especially in conditions where a tethered balloon system is typically deployed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Small molecule modulators of epigenetic processes are currently sought as basic probes for biochemical mechanisms, and as starting points for development of therapeutic agents. N(ε)-Methylation of ...lysine residues on histone tails is one of a number of post-translational modifications that together enable transcriptional regulation. Histone lysine demethylases antagonize the action of histone methyltransferases in a site- and methylation state-specific manner. N(ε)-Methyllysine demethylases that use 2-oxoglutarate as co-factor are associated with diverse human diseases, including cancer, inflammation and X-linked mental retardation; they are proposed as targets for the therapeutic modulation of transcription. There are few reports on the identification of templates that are amenable to development as potent inhibitors in vivo and large diverse collections have yet to be exploited for the discovery of demethylase inhibitors.
High-throughput screening of a ∼236,000-member collection of diverse molecules arrayed as dilution series was used to identify inhibitors of the JMJD2 (KDM4) family of 2-oxoglutarate-dependent histone demethylases. Initial screening hits were prioritized by a combination of cheminformatics, counterscreening using a coupled assay enzyme, and orthogonal confirmatory detection of inhibition by mass spectrometric assays. Follow-up studies were carried out on one of the series identified, 8-hydroxyquinolines, which were shown by crystallographic analyses to inhibit by binding to the active site Fe(II) and to modulate demethylation at the H3K9 locus in a cell-based assay.
These studies demonstrate that diverse compound screening can yield novel inhibitors of 2OG dependent histone demethylases and provide starting points for the development of potent and selective agents to interrogate epigenetic regulation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Age-related differences in working memory (WM) can be large, but the exact sources are unclear. We hypothesized that young adults outperform older adults on WM tasks because they use controlled ...attention processes to prioritize the maintenance of relevant information in WM in a proactive mode, whereas older adults tend to rely on the strength of familiarity signals to make memory decisions in a reactive mode. We used a WM task that cued participants to prioritize one item over others and presented repeated lure probes that cause errors when one is engaged in a reactive mode. Results showed that, relative to young adults with full attention available to use proactive control during the delays, older adults with full attention (and young adults with divided attention) during the delays had exaggerated error rates to repeated lure probes compared to control probes. When the amount of proactive interference was increased (by repeating stimuli across trials), older adults were able to engage in proactive control, and this eliminated their exaggerated error rate (while young adults with divided attention could not). These results provide evidence for a dual mechanisms of control account of age differences in WM.
Public Significance Statement
Age-related differences in working memory (WM) underlie various aspects of older adults' cognitive functioning. This study shows that age-related differences are largely due to older adults' difficulties with focusing attention on relevant information and resisting interference from irrelevant information. Older adults made memory decisions in a reactive-mode by responding based on whether a stimulus seemed familiar; however, with practice and feedback, they shifted to using a proactive mode by maintaining their focus on the to-be-remembered items, and this eliminated their age difference. This study helps to explain age differences in WM and identifies cognitive training targets to improve older adults' cognition.
A systematic review and meta-analysis were conducted to synthesize the existing literature on how transcranial magnetic stimulation (TMS) has been used to modulate episodic memory. Given the numerous ...parameters of TMS protocols and experimental design characteristics that can be manipulated, a mechanistic understanding of how changes in the combination of parameters (e.g., frequency, timing, intensity, targeted brain region, memory task) modulate episodic memory is needed. To address this, we reviewed 59 studies and conducted a meta-analysis on 245 effect sizes from 37 articles on healthy younger adults (
= 1,061). Analyses revealed generally more beneficial effects of 1-Hz rTMS vs. other frequencies on episodic memory. Moderation analyses revealed complex interactions as online 20-Hz rTMS protocols led to negative effects, while offline 20-Hz rTMS led to enhancing effects. There was also an interaction between stimulation intensity and frequency as 20-Hz rTMS had more negative effects when applied below- vs. at-motor threshold. Conversely, 1-Hz rTMS had more beneficial effects than other frequencies when applied below- vs. at- or above-motor threshold. No reliable aggregate or hypothesized interactions were found when assessing stimulation site (frontal vs. parietal cortex, left vs. right hemisphere), stimulated memory process (during encoding vs. retrieval), the type of retrieval (associative/recollection vs. item/familiarity), or the type of control comparison (active vs. sham or no TMS) on episodic memory. However, there is insufficient data to make strong inference based on the lack of aggregate or two-way interactions between these factors, or to assess more complex (e.g., 3-way) interactions. We reviewed the effects on other populations (healthy older adults and clinical populations), but systematic comparison of parameters was also prevented due to insufficient data. A database of parameters and effects sizes is available as an open source repository so that data from studies can be continuously accumulated in order to facilitate future meta-analysis. In conclusion, modulating episodic memory relies on complex interactions among the numerous moderator variables that can be manipulated. Therefore, rigorous, systematic comparisons need to be further investigated as the body of literature grows in order to fully understand the combination of parameters that lead to enhancing, detrimental or null effects on episodic memory.
PDF
