Transient crosslinking kinetics optimize gene cluster interactions

Our understanding of how chromosomes structurally organize and dynamically interact has been revolutionized through the lens of long-chain polymer physics. Major protein contributors to chromosome structure and dynamics are condensin and cohesin that stochastically generate loops within and between chains, and entrap proximal strands of sister chromatids. In this paper, we explore the ability of transient, protein-mediated, gene-gene crosslinks to induce clusters of genes, thereby dynamic architecture, within the highly repeated ribosomal DNA that comprises the nucleolus of budding yeast. We implement three approaches: live cell microscopy; computational modeling of the full genome during G1 in budding yeast, exploring four decades of timescales for transient crosslinks between 5k bp domains in the nucleolus on Chromosome XII; and, temporal network models with automated community detection algorithms applied to the full range of 4D modeling datasets. The data analysis tools detect and track gene clusters, their size, number, persistence time, and their plasticity. Of biological significance, our analysis reveals an optimal mean crosslink lifetime that promotes pairwise and cluster gene interactions through "flexible" clustering. In this state, large gene clusters self-assemble yet frequently interact, marked by gene exchanges between clusters, which in turn maximizes global gene interactions in the nucleolus. This regime stands between two limiting cases each with far less global gene interactions: with shorter crosslink lifetimes, "rigid" clustering emerges with clusters that interact infrequently; with longer crosslink lifetimes, there is a dissolution of clusters. These observations are compared with imaging experiments on a normal yeast strain and two condensin-modified mutant cell strains, applying the same image analysis pipeline to the experimental and simulated datasets

Clinical and Professional Reasoning Development in Level II Fieldwork: Occupational Therapy Assistant Students’ Perception

Occupational therapy academic programs are tasked with preparing occupational therapy assistant (OTA) students to develop and use clinical and professional reasoning in practice. A component of this academic education, Level II fieldwork (FW), develops clinical and professional reasoning by allowing students to practice this skill. Although numerous studies have investigated this topic in occupational therapy students, only one small study has previously investigated this in OTA students during Level II FW. Thus, we designed a mixed methods study of OTA students during Level II FW (n = 58) to confirm and expand our knowledge of learning experiences that develop clinical and professional reasoning skills. Six major aspects of Level II FW were identified by participants as contributing to the development of their clinical and professional reasoning skills: “hands-on experience,” “thinking on your feet,” “the value of community-based placements,” “the supervision approach of the FW educator,” “application of evidence-based practice,” and “interprofessional interactions.” Three of these themes were novel as they did not emerge from the previous study. According to most participants their clinical and professional reasoning development was positively impacted when their FW educator chunked information (88.5%), modeled best practice (84.6%), asked questions (84.6%), or engaged in story-telling (84.6%), with the latter two being perceived as most impactful. The study results suggest that the development of clinical and professional reasoning may be highly individualized and driven by what students experience

Impaired muscle stem cell function in cows with high concentrations of androstenedione in their follicular fluid

It is unclear whether androstenedione (A4) increases muscle mass and strength similar to testosterone or whether it produces primarily catabolic effects on muscle-like estrogen (Rasmussen et al., 2000). Summers et al. (2014) observed two populations of cows that exhibit either high (\u3e40 ng/mL; High A4) or low (\u3c20 ng/mL; Low A4) concentrations of A4 within the fluid of the dominant follicle just prior to ovulation. High A4 cows had decreased reproductive rates and shorter times before falling out of the herd, but those that did produce calves weaned them ~10-kg heavier than their low A4 counterparts (Summers et al., 2014). It appears that the difference in weights is due to faster growing and more efficient skeletal muscle. High A4 cows share many characteristics with women suffering from polycystic ovary syndrome (PCOS), whose high levels of circulating androgens are associated with changes in body composition (Kirchengast and Huber, 2001)

Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and nonusers

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater DA synthesis capacity than NC participants, particularly in dorsal caudate, and greater cognitive flexibility. Furthermore, across individuals, the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or DA release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women\u27s hormone status. Hormonal contraception (in the form of pill, shot, implant, ring, or intrauterine device) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the DA system. Findings from this study begin to address this critical gap in women\u27s health

Self-Reported Cognitive Function and Mental Health Diagnoses among Former Professional American-Style Football Players

Clinical practice strongly relies on patients' self-report. Former professional American-style football players are hesitant to seek help for mental health problems, but may be more willing to report cognitive symptoms. We sought to assess the association between cognitive symptoms and diagnosed mental health problems and quality of life among a cohort of former professional players. In a cross-sectional design, we assessed self-reported cognitive function using items from the Quality of Life in Neurological Disorders (Neuro-QOL) Item Bank. We then compared mental health diagnoses and quality of life, assessed by items from the Patient-Reported Outcome Measurement Information System (PROMIS ®), between former professional players reporting daily problems in cognitive function and former players not reporting daily cognitive problems. Of the 3758 former professional players included in the analysis, 40.0% reported daily problems due to cognitive dysfunction. Former players who reported daily cognitive problems were more likely to also report depression (18.0% vs. 3.3%, odds ratio [OR] = 6.42, 95% confidence interval [CI] [4.90-8.40]) and anxiety (19.1% vs. 4.3%, OR = 5.29, 95% CI [4.14-6.75]) than those without daily cognitive problems. Further, former players reporting daily cognitive problems were more likely to report memory loss and attention deficit(/hyperactivity) disorder and poorer general mental health, lower quality of life, less satisfaction with social activities and relationships, and more emotional problems. These findings highlight the potential of an assessment of cognitive symptoms for identifying former players with mental health, social, and emotional problems

The Grizzly, November 9, 2006

Philly Soft Pretzel Factory Now Open • English for All • WeCAN Make(s) a Difference! Workers\u27 Rights Conference Held at Ursinus • Wearing Justice on Our Sleeves • Students Protest at the Mall • Genital Warts and HPV: The Facts, Part I • Spotlight: Psychology Club • Guy Fawkes Day Revisited • Triangle People : The Work of Lynn Chadwick • Opinions: The Significance of Kyke ; Open Letter to Ursinus; 2008 Preview: Part II; Gay Marriage: Who Should Decide? • Bears Beat Rival LaSalle, Take Home Second Title • Explosive Offense Shoots Bears Past Diplomatshttps://digitalcommons.ursinus.edu/grizzlynews/1724/thumbnail.jp

Clinical Characteristics Associated with Bacterial Bloodstream Coinfection in COVID-19

INTRODUCTION: Inappropriate antibiotic use in COVID-19 is often due to treatment of presumed bacterial coinfection. Predictive factors to distinguish COVID-19 from COVID-19 with bacterial coinfection or bloodstream infection are limited. METHODS: We conducted a retrospective cohort study of 595 COVID-19 patients admitted between March 8, 2020, and April 4, 2020, to describe factors associated with a bacterial bloodstream coinfection (BSI). The primary outcome was any characteristic associated with BSI in COVID-19, with secondary outcomes including 30-day mortality and days of antibiotic therapy (DOT) by antibiotic consumption (DOT/1000 patient-days). Variables of interest were compared between true BSI (n = 25) and all other COVID-19 cases (n = 570). A secondary comparison was performed between positive blood cultures with true BSI (n = 25) and contaminants (n = 33) on antibiotic use. RESULTS: Fever (\u3e 38 °C) (as a COVID-19 symptom) was not different between true BSI (n = 25) and all other COVID-19 patients (n = 570) (p = 0.93), although it was different as a reason for emergency department (ED) admission (p = 0.01). Neurological symptoms (ED reason or COVID-19 symptom) were significantly higher in the true BSI group (p \u3c 0.01, p \u3c 0.01) and were independently associated with true BSI (ED reason: OR = 3.27, p \u3c 0.01; COVID-19 symptom: OR = 2.69, p = 0.03) on multivariate logistic regression. High (15-19.9 × 10(9)/L) white blood cell (WBC) count at admission was also higher in the true BSI group (p \u3c 0.01) and was independently associated with true BSI (OR = 2.56, p = 0.06) though was not statistically significant. Thirty-day mortality was higher among true BSI (p \u3c 0.01). Antibiotic consumption (DOT/1000 patient-days) between true BSI and contaminants was not different (p = 0.34). True bloodstream coinfection was 4.2% (25/595) over the 28-day period. CONCLUSION: True BSI in COVID-19 was associated with neurological symptoms and nonsignificant higher WBC, and led to overall higher 30-day mortality and worse patient outcomes

Unveiling the Phase Transition of the Universe During the Reionization Epoch with Lyman-alpha

The epoch of reionization (6 < z < 10) marks the period in our universe when the first large galaxies grew to fruition, and began to affect the universe around them. Massive stars, and potentially accreting supermassive black holes, filled the universe with ionizing radiation, burning off the haze of neutral gas that had filled the intergalactic medium (IGM) since recombination (z~1000). The evolution of this process constrains key properties of these earliest luminous sources, thus observationally constraining reionization is a key science goal for the next decade. The measurement of Lyman-alpha emission from photometrically-identified galaxies is a highly constraining probe of reionization, as a neutral IGM will resonantly scatter these photons, reducing detectability. While significant work has been done with 8-10m telescopes, these observations require extremely large telescopes (ELTs); the flux limits available from today's 10m class telescopes are sufficient for only the brightest known galaxies (m < 26). Ultra-deep surveys with the Giant Magellan Telescope (GMT) and Thirty Meter Telescope (TMT) will be capable of detecting Lyman-alpha emission from galaxies 2-3 magnitudes fainter than today's deepest surveys. Wide-field fiber spectroscopy on the GMT combined with narrow-field AO-assisted slit spectroscopy on the TMT will be able to probe the expected size of ionized bubbles throughout the epoch of reionization, following up degree scale deep imaging surveys with the Wide Field Infrared Space Telescope. These data will provide the first resolved Lyman-alpha-based maps of the ionized intergalactic medium throughout the epoch of reionization, constraining models of both the temporal and spatial evolution of this phase change.Comment: White paper submitted to the Astro2020 Decadal Review of the National Academy of Science

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap