Histone variants and epigenetics Henikoff, Steven; Smith, M Mitchell
Cold Spring Harbor perspectives in biology,
01/2015, Letnik:
7, Številka:
1
Journal Article
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Histones package and compact DNA by assembling into nucleosome core particles. Most histones are synthesized at S phase for rapid deposition behind replication forks. In addition, the replacement of ...histones deposited during S phase by variants that can be deposited independently of replication provide the most fundamental level of chromatin differentiation. Alternative mechanisms for depositing different variants can potentially establish and maintain epigenetic states. Variants have also evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, and other processes. Investigations into the evolution, structure, and metabolism of histone variants provide a foundation for understanding the participation of chromatin in important cellular processes and in epigenetic memory.
PURPOSETo investigate the effects of mental fatigue on soccer-specific physical and technical performance.
METHODSThis investigation consisted of two separate studies. Study 1 assessed the ...soccer-specific physical performance of 12 moderately trained soccer players using the Yo-Yo Intermittent Recovery Test, Level 1 (Yo-Yo IR1). Study 2 assessed the soccer-specific technical performance of 14 experienced soccer players using the Loughborough Soccer Passing and Shooting Tests (LSPT, LSST). Each test was performed on two occasions and preceded, in a randomized, counterbalanced order, by 30 min of the Stroop task (mentally fatiguing treatment) or 30 min of reading magazines (control treatment). Subjective ratings of mental fatigue were measured before and after treatment, and mental effort and motivation were measured after treatment. Distance run, heart rate, and ratings of perceived exertion were recorded during the Yo-Yo IR1. LSPT performance time was calculated as original time plus penalty time. LSST performance was assessed using shot speed, shot accuracy, and shot sequence time.
RESULTSSubjective ratings of mental fatigue and effort were higher after the Stroop task in both studies (P < 0.001), whereas motivation was similar between conditions. This mental fatigue significantly reduced running distance in the Yo-Yo IR1 (P < 0.001). No difference in heart rate existed between conditions, whereas ratings of perceived exertion were significantly higher at iso-time in the mental fatigue condition (P < 0.01). LSPT original time and performance time were not different between conditions; however, penalty time significantly increased in the mental fatigue condition (P = 0.015). Mental fatigue also impaired shot speed (P = 0.024) and accuracy (P < 0.01), whereas shot sequence time was similar between conditions.
CONCLUSIONSMental fatigue impairs soccer-specific running, passing, and shooting performance.
A critical technique for understanding how neuronal activity contributes to behavior is determining whether perturbing it changes behavior. The advent of optogenetic techniques allows the immediately ...reversible alteration of neuronal activity in contrast to chemical approaches lasting minutes to hours. Modification of behavior using optogenetics has had substantial success in rodents but has not been as successful in monkeys. Here, we show how optogenetic inactivation of superior colliculus neurons in awake monkeys leads to clear and repeatable behavioral deficits in the metrics of saccadic eye movements. We used our observations to evaluate principles governing the use of optogenetic techniques in the study of the neuronal bases of behavior in monkeys, particularly how experimental design must address relevant parameters, such as the application of light to subcortical structures, the spread of viral injections, and the extent of neuronal inactivation with light.
► Optogenetic techniques modulate behavior in nonhuman primates as they do in rodents ► Precise saccadic deficits followed optogenetic inactivation of superior colliculus ► Deficit size resulted from interaction of viral and light spread in groups of neurons ► Immediate and reversible effects provide critical tools for primate circuit analysis
Optogenetic techniques provide a temporally and spatially precise method for modulating neuronal activity. Cavanaugh et al. apply these methods to specific motor circuits to successfully alter eye movements in the nonhuman primate, revealing certain principles and constraints of such techniques.
PURPOSEThe purpose of the study was to investigate the effects of mental fatigue on intermittent running performance.
METHODSTen male intermittent team sports players performed two identical ...self-paced, intermittent running protocols. The two trials were separated by 7 d and preceded, in a randomized-counterbalanced order, by 90 min of either emotionally neutral documentaries (control) or the AX-continuous performance test (AX-CPT; mental fatigue). Subjective ratings of fatigue and vigor were measured before and after these treatments, and motivation was recorded before the intermittent running protocol. Velocity, heart rate, oxygen consumption, blood glucose and lactate concentrations, and ratings of perceived exertion (RPE) were measured throughout the 45-min intermittent running protocol. Session RPE was recorded 30 min after the intermittent running protocol.
RESULTSSubjective ratings of fatigue were higher after the AX-CPT (P = 0.005). This mental fatigue significantly reduced velocity at low intensities (1.28 ± 0.18 m·s vs 1.31 ± 0.17 m·s; P = 0.037), whereas high-intensity running and peak velocities were not significantly affected. Running velocity at all intensities significantly declined over time in both conditions (P < 0.001). Oxygen consumption was significantly lower in the mental fatigue condition (P = 0.007). Other physiological variables, vigor and motivation, were not significantly affected. Ratings of perceived exertion during the intermittent running protocol were not significantly different between conditions despite lower overall velocity in the mental fatigue condition. Session RPE was significantly higher in the mental fatigue condition (P = 0.013).
CONCLUSIONMental fatigue impairs intermittent running performance. This negative effect of mental fatigue seems to be mediated by higher perception of effort.
This investigation assessed the impact of three cognitively demanding tasks on cognitive performance, subjective, and physiological indicators of mental fatigue. Following familiarization, ...participants completed four testing sessions, separated by 48 h. During each session, participants watched a 45-min emotionally neutral documentary (control) or completed one of the following computer tasks: Psychomotor Vigilance Task (PVT); AX-Continuous Performance Test (AX-CPT); or Stroop Task. Mental fatigue was assessed before and at regular periods for 60 min following the 45-min treatments. Cognitive performance was assessed using 3-min PVT, and task performance. Subjective assessments were conducted using the Brunel Mood Scale, and visual analog scales (VAS). Physiological indicators of mental fatigue included electroencephalography (EEG), and heart rate variability (HRV). Subjective ratings of mental fatigue increased from pre to 0-min post in all-treatments, but not the documentary (p < 0.05). Subjective fatigue (VAS) remained higher (p < 0.05) than pretreatment values for 20-, 50-, and 60-min following the PVT, Stroop, and AX-CPT respectively. The cognitively demanding tasks had unclear effects on 3-min PVT, EEG, and HRV assessments. Tasks requiring response inhibition appear to induce fatigue for longer durations than a simple vigilance task. Simple VAS appear to be the most practical method for assessing mental fatigue.
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Electrochemical jet processing techniques have traditionally been considered to be limited to planar interactions with the electrolyte jet being maintained normal to the workpiece ...surface. In this study, the viability and resultant effects of articulating the nozzle relative to the work were investigated for the first time. Two machining conventions were defined, normal, where the jet is maintained perpendicular to the traverse direction, and push/pull, where the nozzle is rotated with respect to the direction of travel. It was found, with the normal convention that a range of differing resultant profile surface geometries could be created; unique to this process. This was demonstrated by the changing resultant side wall slopes found through the rotation of the head with up to 80% difference between the slopes of the cut walls. The adjacent wall to the nozzle slope decreasing as the jet angle approaches 90° whilst the opposite side wall slope increases. Predictable ratios of the differing slopes of the striation side walls were then able to be defined. The push/pull convention demonstrated that deeper, sharper cuts are possible due to the highly localising current density effect of nozzle inclination achieving a 35% increase in depth without requiring additional energy. Also, that resultant surface finish could be greatly improved, reducing the profile roughness (Ra) from 0.2 μm in the pull mode to 0.04 μm in the push mode achieving a mirror-like finish. The mechanics of these phenomena are investigated and defined. The influence of nozzle jet speed variation combined with inclining the jet was also studied. This was found to have no noticeable influence on the resultant profile when the nozzle is inclined. In contrast, when the nozzle is normal to the surface, jet velocity is seen to have a direct influence due to polarisation effects relating to the poor clearance of machining debris and the formation of oxides. It is shown that through variation of the angle of jet address an extra level of flexibility and performance is possible within electrochemical jet processes.
Objectives: The relationship between task constraints and player behaviors is of interest to coaches tasked with designing practice to optimize learning. This study aims to compare the skill ...involvements and cooperative team behavior of teams of youth soccer players engaged in a goal exaggeration and/or a prescriptive coach instruction condition compared to a free-play control condition. Methods: Twenty male soccer players aged 12-15 participated in small-sided games under four conditions: free-play, goal exaggeration, prescriptive coach instruction, and combination over four weeks. Using video footage, teams' collective skill involvements (shot, pass, dribble) and passing network characteristics (closeness, density, and betweenness) were measured for each game. Results: A Friedmans rank test identified that playing conditions resulted in significant differences in attempted dribbles (p < .001), goals scored (p < .001), network density (p = .001), closeness (p < .001) and betweenness (p = .002). Teams attempted to dribble the most in the free-play and goal-exaggeration conditions, and the most goals were scored in the goal-exaggeration and combination conditions. Additionally, teams exhibited more well-connected passing networks (i.e. higher density, higher closeness, and lower betweenness values) in the combination condition and higher network density in the explicit instruction condition. Conclusions: The results of this study indicate that coach instruction may be more associated with cooperative team behavior, whereas free-play or manipulating task constraints in the absence of instruction may be associated with players attempting more individual actions.Objectives: The relationship between task constraints and player behaviors is of interest to coaches tasked with designing practice to optimize learning. This study aims to compare the skill involvements and cooperative team behavior of teams of youth soccer players engaged in a goal exaggeration and/or a prescriptive coach instruction condition compared to a free-play control condition. Methods: Twenty male soccer players aged 12-15 participated in small-sided games under four conditions: free-play, goal exaggeration, prescriptive coach instruction, and combination over four weeks. Using video footage, teams' collective skill involvements (shot, pass, dribble) and passing network characteristics (closeness, density, and betweenness) were measured for each game. Results: A Friedmans rank test identified that playing conditions resulted in significant differences in attempted dribbles (p < .001), goals scored (p < .001), network density (p = .001), closeness (p < .001) and betweenness (p = .002). Teams attempted to dribble the most in the free-play and goal-exaggeration conditions, and the most goals were scored in the goal-exaggeration and combination conditions. Additionally, teams exhibited more well-connected passing networks (i.e. higher density, higher closeness, and lower betweenness values) in the combination condition and higher network density in the explicit instruction condition. Conclusions: The results of this study indicate that coach instruction may be more associated with cooperative team behavior, whereas free-play or manipulating task constraints in the absence of instruction may be associated with players attempting more individual actions.
By tethering their circular genomes (episomes) to host chromatin, DNA tumor viruses ensure retention and segregation of their genetic material during cell divisions. Despite functional genetic and ...crystallographic studies, there is little information addressing the 3D structure of these tethers in cells, issues critical for understanding persistent infection by these viruses. Here, we have applied direct stochastic optical reconstruction microscopy (dSTORM) to establish the nanoarchitecture of tethers within cells latently infected with the oncogenic human pathogen, Kaposi’s sarcoma-associated herpesvirus (KSHV). Each KSHV tether comprises a series of homodimers of the latency-associated nuclear antigen (LANA) that bind with their C termini to the tandem array of episomal terminal repeats (TRs) and with their N termini to host chromatin. Superresolution imaging revealed that individual KSHV tethers possess similar overall dimensions and, in aggregate, fold to occupy the volume of a prolate ellipsoid. Using plasmids with increasing numbers of TRs, we found that tethers display polymer power law scaling behavior with a scaling exponent characteristic of active chromatin. For plasmids containing a two-TR tether, we determined the size, separation, and relative orientation of two distinct clusters of bound LANA, each corresponding to a single TR. From these data, we have generated a 3D model of the episomal half of the tether that integrates and extends previously established findings from epifluorescent, crystallographic, and epigenetic approaches. Our findings also validate the use of dSTORM in establishing novel structural insights into the physical basis of molecular connections linking host and pathogen genomes.
microRNA mimics are synthetic RNA molecules that imitate the mature miRNA duplexes and their functions. These mimics have shown promise in treating cancers. Nucleotide chemical modifications of ...microRNA mimics have been investigated and have improved the stability of miRNA mimics. However, the potential therapeutic benefit of mimic analogs based on sequence modifications has not been explored. miR-506-3p was identified as a differentiation-inducing microRNA in neuroblastoma cells, suggesting the potential of applying the miR-506-3p mimic in neuroblastoma differentiation therapy. In this study, we explored the possibility of developing shortened miR-506-3p analogs that can maintain differentiation-inducing activities comparable to the wild-type miR-506-3p mimic. We found that deleting up to two nucleotides at either the 3′ end or within the middle region of the miR-506-3p sequence fully maintained the differentiation-inducing activity when compared to the wild-type mimic. Deleting up to four nucleotides from the 3′ end or deleting three nucleotides in the middle positions diminished the differentiation-inducing activity, but the analogs still maintained differentiation-inducing activities that were significantly higher than the negative control oligo. The shortened analog designs potentially benefit patients from two perspectives: (1) the reduced cost of manufacturing shortened analogs, and (2) the reduced non-specific toxicity due to their smaller molecular sizes.
The increasing demand for optimised component surfaces with enhanced chemical and geometric complexity is a key driver in the manufacturing technology required for advanced surface production. ...Current methodologies cannot create complex surfaces in an efficient and scalable manner in robust engineering materials. Hence, there is a need for advanced manufacturing technologies which overcome this. Current technologies are limited by resolution, geometric flexibility and mode of energy delivery. By addressing the fundamental limitations of electrochemical jetting techniques through modulation of the current density distribution by mechanical design, significant improvements to the electrochemical jet process methods are presented. A simplified 2D stochastic model was developed with the ability to vary current density distribution to assess the effects of nozzle-tip shape changes. The simulation demonstrated that the resultant profile was found to be variable from that of a standard nozzle. These nozzle-tip modifications were then experimentally tested finding a high degree of variance was possible in the machined profile. Improvements such as an increase in side-wall steepness of 162% are achieved over a standard profile, flat bases to the cut profile and a reduction of profile to surface inter-section radius enable the process to be analogous to traditional milling profiles. Since electrode design can be rapidly modified EJP is shown to be a flexible process capable of varied and complex meso-scale profile creation. Innovations presented here in the modulation of resistance in-jet have enabled electrochemical jet processes to become a viable, top-down, single-step method for applying complex surfaces geometries unachievable by other means.
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•Significant advances are made to the flexibility of EJP in creating meso-scale surface features.•Geometric modifications to the nozzle aperture allows modulation of in-jet resistance.•Results demonstrate a large controllable variation in cut profile.•Simulations enable close prediction of the corresponding response profile.•The design impact factor (DIF) is developed to inform future nozzle design.
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