Reverse Recruitment: Activation of Yeast Genes at the Nuclear Periphery

The regulation of genes at the nuclear periphery is an evolutionarily conserved phenomenon in eukaryotes. The reverse-recruitment model of transcriptional activation postulates that genes are activated by moving to and contacting transcription machinery located at subnuclear structures. In Saccharomyces cerevisiae it has been reported that this platform for gene regulation may reside at the nuclear periphery. To test this hypothesis, I utilized a GFP-gene tagging technique, which uses LacI-GFP to visualize a tandem array of its DNA-binding sequence, to monitor localization ofSUC2 and GALL I found that both genes preferentially localized to the nuclear periphery when transcriptionally active. By developing an in vivo single cell reporter assay, I simultaneously monitored gene location and expression of a GFP-Ras2 reporter and found that, when induced, cells with perinuclear GAL genes activated transcription 10 minutes before cells with genes localized to the nucleoplasm. Thus, interaction with the nuclear periphery correlates with more rapid initiation. Further, the GAL1 gene can anchor in response to galactose, even when transcription is blocked, suggesting that genes move to the nuclear periphery prior to transcriptional initiation. I also show that gene localization to the nuclear periphery correlates with defects in regulation caused by the removal of SUC2 and GAL1 regulatory factors. Strikingly, these factors can be biochemically purified with the perinuclear compartment. Further, I report here that components of the transcriptional pre-initiation complex are localized to the nuclear periphery in the presence or absence of transcription. This suggests that there is a highly organized subnuclear architecture that facilitates gene regulation at the nuclear periphery. Interestingly, I saw that the archetypal transcriptional activator Gal4 exhibits a quantifiable difference in its subnuclear mobility that correlates with its function. For example, induced Gal4 shifts to a more slowly mobile form. I hypothesize that this shift may be the result of interaction with perinuclear transcription factories and that the well-characterized dimerization and activation domains of Gal4 play a role in this tethering. Finally, I propose a model by which chromatin structure can influence gene movement to the nuclear periphery through the dynamic conversion between heterochromatin and euchromatin

The Nuclear Pore Complex Mediates Binding of the Mig1 Repressor to Target Promoters

All eukaryotic cells alter their transcriptional program in response to the sugar glucose. In Saccharomyces cerevisiae, the best-studied downstream effector of this response is the glucose-regulated repressor Mig1. We show here that nuclear pore complexes also contribute to glucose-regulated gene expression. NPCs participate in glucose-responsive repression by physically interacting with Mig1 and mediating its function independently of nucleocytoplasmic transport. Surprisingly, despite its abundant presence in the nucleus of glucose-grown nup120Δ or nup133Δ cells, Mig1 has lost its ability to interact with target promoters. The glucose repression defect in the absence of these nuclear pore components therefore appears to result from the failure of Mig1 to access its consensus recognition sites in genomic DNA. We propose that the NPC contributes to both repression and activation at the level of transcription

Differential Effects of Emotional Information on Interference Task Performance Across the Life Span

While functioning in multiple domains declines with age, emotional regulation appears to remain preserved in older adults. The Emotion Inhibition (Emotional Stroop) Test requires participants to name the ink color in which neutrally and emotionally valenced words are printed. It was employed in the current investigation as a measure of affective regulation in the context of an interference task in relation to age. Results demonstrated that while participants ranging from 20 to 50 years of age performed significantly worse on the emotion Stroop Inhibition relative to the neutral Stroop Inhibition condition, subjects over 60 years of age displayed the converse of this pattern, performing better on the emotion than the neutral condition, suggesting that they are less affected by the emotional impact of the positive and negative words used in the former condition. This pattern of age-related change in the ability to manage emotion may be related to blunting of affective signaling in limbic structures or, at the psychological level, focusing on emotional regulation

Applications of the Critical Power Model to Dynamic Constant External Resistance Exercise: A Brief Review of the Critical Load Test

The study and application of the critical power (CP) concept has spanned many decades. The CP test provides estimates of two distinct parameters, CP and W0 , that describe aerobic and anaerobic metabolic capacities, respectively. Various mathematical models have been used to estimate the CP and W0 parameters across exercise modalities. Recently, the CP model has been applied to dynamic constant external resistance (DCER) exercises. The same hyperbolic relationship that has been established across various continuous, whole-body, dynamic movements has also been demonstrated for upper-, lower-, and whole-body DCER exercises. The asymptote of the load versus repetition relationship is defined as the critical load (CL) and the curvature constant is L0 . The CL and L0 can be estimated from the same linear and non-linear mathematical models used to derive the CP. The aims of this review are to (1) provide an overview of the CP concept across continuous, dynamic exercise modalities; (2) describe the recent applications of the model to DCER exercise; (3) demonstrate how the mathematical modeling of DCER exercise can be applied to further our understanding of fatigue and individual performance capabilities; and (4) make initial recommendations regarding the methodology for estimating the parameters of the CL test

Intimate Partner Violence Screening and Implications for Health Care Providers

Abstract: Purpose: The purpose of this literature review is to (1) present research on current IPV screening prevalence within the medical community, (2) emphasize the importance of IPV screening for physical therapists,(3) identify barriers that exist to IPV screening, (4) examine current teaching methods for IPV within healthcare curriculums and (5) identify valid and reliable IPV screening tools for clinical application. Description: A comprehensive literature search on six different databases was completed from September 2012 to March 2014. Search terms included intimate partner violence (IPV), domestic violence, health providers and IPV screening tools. Randomized control trials were included if they evaluated at least one IPV screening tool utilized in the study. Three independent reviewers screened 5664 results and identified 55 relevant research studies. Summary of Use: Five studies were excluded due to poor quality research data or design. Despite the established importance of IPV screening by healthcare professionals, the research has demonstrated that healthcare professionals are not providing universal screening for all patients. Only 8% of physical therapists routinely screen for IPV. Challenges exist in the healthcare field in the screening of patients for IPV: including (1) differing cultural perspectives on IPV, (2) time constraints, (3) language barriers, (4) lack of knowledge and (5) healthcare practitioners negative perceptions.The most frequent provider-related barriers included “lack of provider education regarding IPV, lack of time, and lack of effective interventions. PREMIS (Physician Readiness to Manage Intimate Partner Violence Survey) is a 15 minute survey that Short et al. found to have good internal consistency and reliability (Cronbach’s alpha ≥ 0.65). PREMIS is more current and comprehensive than previous standardized IPV assessment tools and can easily be utilized by physical therapists. Importance to Members: IPV is a major public health concern with a healthcare cost of nearly $4.1 billion and affects nearly 1/3 of women during their lifetime. Three recommendations can be made for physical therapists based on various models for IPV education. 1) Experiential learning, 2) Utilize APTA’s Blueprint for Teaching Cultural Competence applying it to IPV screening, and 3) Utilization of the PREMIS tool by physical therapists to assess IPV. The prevalence of IPV and the lack of physical therapist IPV screening, calls for an evaluation of the requirements and screening tools available for physical therapists in the clinic. By improving education for IPV screening, new clinicians can be better prepared for detecting and reporting IPV once they are practicing physical therapists. Research is limited concerning the methods by which physical therapists are instructed in IPV screening

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie- affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination

An evaluation of the epidemiology of medication discrepancies and clinical significance of medicines reconciliation in children admitted to hospital.

To determine the incidence of unintended medication discrepancies in paediatric patients at the time of hospital admission; evaluate the process of medicines reconciliation; assess the benefit of medicines reconciliation in preventing clinical harm

Individual Responses for Muscle Activation, Repetitions, and Volume during Three Sets to Failure of High- (80% 1RM) \u3ci\u3eversus\u3c/i\u3e Low-Load (30% 1RM) Forearm Flexion Resistance Exercise

This study compared electromyographic (EMG) amplitude, the number of repetitions completed, and exercise volume during three sets to failure of high- (80% 1RM) versus low-load (30% 1RM) forearm flexion resistance exercise on a subject-by-subject basis. Fifteen men were familiarized, completed forearm flexion 1RM testing. Forty-eight to 72 h later, the subjects completed three sets to failure of dumbbell forearm flexion resistance exercise with 80% (n = 8) or 30% (n = 7) 1RM. EMG amplitude was calculated for every repetition, and the number of repetitions performed and exercise volume were recorded. During sets 1, 2, and 3, one of eight subjects in the 80% 1RM group demonstrated a significant linear relationship for EMG amplitude versus repetition. For the 30% 1RM group, seven, five, and four of seven subjects demonstrated significant linear relationships during sets 1, 2, and 3, respectively. The mean EMG amplitude responses show that the fatigue-induced increases in EMG amplitude for the 30% 1RM group and no change in EMG amplitude for the 80% 1RM group resulted in similar levels of muscle activation in both groups. The numbers of repetitions completed were comparatively greater, while exercise volumes were similar in the 30% versus 80% 1RM group. Our results, in conjunction with those of previous studies in the leg extensors, suggest that there may be muscle specific differences in the responses to high- versus low-load exercise

The effects of anatabine on non-invasive indicators of muscle damage: a randomized, double-blind, placebo-controlled, crossover study

Background: Anatabine (ANA), a minor tobacco alkaloid found in the Solanaceae family of plants, may exhibit anti-inflammatory activity, which may be useful to aid in recovery from exercise-induced muscle damage. The purpose of this study, therefore, was to examine the effects of ANA supplementation on the recovery of isometric strength and selected non-invasive indicators of muscle damage. Methods: A double-blinded, placebo-controlled, crossover design was used to study eighteen men (mean ± SD age = 22.2 ± 3.1 yrs; body mass = 80.3 ± 15.7 kg) who participated in two randomly-ordered conditions separated by a washout period. The ANA condition consisted of consuming 6–12 mg anatabine per day for 10 days, while testing took place during days 7–10. The placebo (PLA) condition was identical except that the PLA supplement contained no ANA. Maximal voluntary isometric peak torque (PT) of the forearm flexors, arm circumference, hanging joint angle, and subjective pain ratings were measured before (PRE), immediately after (POST), and 24, 48, and 72 h after six sets of 10 maximal, eccentric isokinetic forearm flexion muscle actions. Resting heart rate and blood pressure were measured at PRE and 72 h in each condition. Results: For PT, hanging joint angle, arm circumference, and subjective pain ratings, there were no condition x time (p \u3e 0.05) interactions, there were no main effects for condition (p \u3e 0.05), but there were main effects for time (p \u3c 0.001). There were no condition x time (p \u3e 0.05) interactions and no main effects for condition (p \u3e 0.05) or time (p \u3e 0.05) for blood pressure or resting heart rate. Conclusions: ANA supplementation had no effect on the recovery of muscle strength, hanging joint angle, arm swelling, or subjective pain ratings after a bout of maximal eccentric exercise in the forearm flexors. Therefore, ANA may not be beneficial for those seeking to improve recovery from heavy eccentric exercise. Future studies should examine the effects of ANA on the pro-inflammatory cytokine responses to exercise-induced muscle damage and the chronic low-grade inflammation observed in obese and elderly individuals