Defining functional DNA elements in the human genome Kellis, Manolis; Wold, Barbara; Snyderd, Michael P. ...
Proceedings of the National Academy of Sciences - PNAS,
04/2014, Letnik:
111, Številka:
17
Journal Article
Recenzirano
Odprti dostop
With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the ...Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease.
Consumer demand for commercially prepared plant-based (PB) dog food is increasing, but studies evaluating the short- or long-term effects of PB diets on canine health are lacking. The objective of ...this study was to assess the short-term amino acid (AA), clinicopathologic, and echocardiographic findings in 34 client-owned dogs fed a commercial extruded plant-based diet (PBD) in which pea protein was the primary protein source and 4 control dogs fed a commercial extruded traditional diet (TD). Plasma AA and whole blood taurine concentrations were measured in dogs at baseline and after 4 weeks on the PBD or the TD. Hematologic, serum biochemical, and echocardiographic testing were performed at baseline and after 12 weeks on the PBD or the TD. Four dogs in the PBD group did not complete the study. All essential AAs, except methionine, were higher in dogs after 4 weeks on the PBD compared to baseline. Taurine (plasma and whole blood) was also higher after 4 weeks on the PBD compared to baseline. A meaningful difference was detected in whole blood taurine between the PBD group and the control group at 4 weeks (P = .026) with the PBD group being higher. Median hematologic and biochemical results for the PBD group were within normal limits at baseline and at 12 weeks. In the PBD group, left ventricular internal diastolic dimension (LVIDd, P = < .001) and normalized LVIDd (P = .031) were higher 12 weeks post-PBD compared to baseline. There were no meaningful differences in left ventricular internal systolic dimension (LVIDs), normalized LVIDs, or fractional shortening 12 weeks post-PBD. There was no statistical evidence of difference between the 2 groups of dogs for any of the echocardiographic parameters at baseline or at 12 weeks. Essential AA or taurine deficiency was not observed in this cohort of dogs fed a commercial extruded PBD. Additionally, clinically relevant hematologic, serum biochemical and echocardiographic alterations were not detected. Further research is required to determine if long-term static feeding of PB diets can meet and maintain AA and other nutrient targets in dogs.
Human morphology is a critical component of dental and medical graduate training. Innovations in basic science teaching methods are needed to keep up with an ever-changing landscape of technology. ...The purpose of this study was to investigate whether students in a medical and dental histology course would have better grades if they used gaming software Kahoot® and whether gamification effects on learning and enjoyment.
In an effort to both evoke students' interest and expand their skill retention, an online competition using Kahoot® was implemented for first-year students in 2018 (n = 215) at the University of Eastern Finland. Additionally, closed (160/215) or open-ended (41/215) feedback questions were collected and analyzed.
The Kahoot® gamification program was successful and resulted in learning gains. The overall participant satisfaction using Kahoot® was high, with students (124/160) indicating that gamification increased their motivation to learn. The gaming approach seemed to enable the students to overcome individual difficulties (139/160) and to set up collaboration (107/160); furthermore, gamification promoted interest (109/160), and the respondents found the immediate feedback from senior professionals to be positive (146/160). In the open-ended survey, the students (23/41) viewed collaborative team- and gamification-based learning positively.
This study lends support to the use of gamification in the teaching of histology and may provide a foundation for designing a gamification-integrated curriculum across healthcare disciplines.
Around 88 large vertebrate taxa disappeared from Sahul sometime during the Pleistocene, with the majority of losses (54 taxa) clearly taking place within the last 400,000 years. The largest was the ...2.8-ton browsing Diprotodon optatum, whereas the ~100- to 130-kg marsupial lion, Thylacoleo carnifex, the world's most specialized mammalian carnivore, and Varanus priscus, the largest lizard known, were formidable predators. Explanations for these extinctions have centered on climatic change or human activities. Here, we review the evidence and arguments for both. Human involvement in the disappearance of some species remains possible but unproven. Mounting evidence points to the loss of most species before the peopling of Sahul (circa 50-45 ka) and a significant role for climate change in the disappearance of the continent's megafauna.
In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been ...peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
The study's purpose was to measure the impact of anti-reflux needleless connector usage in prevention of intraluminal thrombotic occlusions among central venous catheters, as represented by alteplase usage, in a home infusion patient population.
An18-month before-and-after cohort study of a single home infusion intervention was conducted to compare occlusion outcomes with use of two types of needleless connectors-neutral and anti-reflux-in preventing catheter occlusions, which have been reported to occur in 28% of home infusion patients, resulting in treatment delays, increased nursing encounters and emergency room visits, and higher overall pharmacy costs for supplies and alteplase.
A total of 552,707 patient therapy days were studied: 42.5% in the neutral needleless connector group (n = 235,004 therapy days) and 57.5% in the anti-reflux needleless connector group (n = 317,703 therapy days). The rate of alteplase usage with neutral versus anti-reflux needleless connectors was 4.4% versus 2.2% per 1,000 therapy days, with median alteplase use of 112 (95% CI, 89-169) units versus 82 (95% CI, 68-109) units (P < 0.001). Implementation of anti-reflux connectors reduced occlusions and alteplase usage by 48%.
Statistical evidence demonstrated that use of anti-reflux needleless connectors with central venous access devices reduced the need for alteplase in the study population. Since 10% of patient occlusions were within 7 days after home infusion admission, future research may indicate that placement of anti-reflux needleless connectors at the time of in-hospital insertion can improve patient outcomes. This quality improvement measure reduced central catheter occlusions, alteplase costs, and the number of required nursing and emergency room visits.
Accurate radiocarbon dating of marine samples requires knowledge of the marine radiocarbon reservoir effect. This effect for a particular site/region is generally assumed constant through time when ...calibrating marine 14C ages. However, recent studies have shown large temporal variations of several hundred to a couple of thousand years in this effect for a number of regions during the late Quaternary and Holocene. Here we report marine radiocarbon reservoir correction (ΔR) for Heron Reef and Moreton Bay in southwestern (SW) Pacific for the last 8 ka derived from 14C analysis of 230Th-dated corals. Most of our ΔR for the last ∼5.4 ka agree well with their modern value, but large ΔR variability of ∼410 yr (from trough to peak) with possible decadal/centennial fluctuations is evident for the period ∼5.4–8 ka. The latter time interval also has significant variations with similar features in previously published ΔR values for other sites in the Pacific, including southern Peru–northern Chile in southeastern (SE) Pacific, the South China Sea, Vanuatu and Papua New Guinea, with the largest magnitude of ∼920 yr from SE Pacific. The mechanisms for these large ΔR variations across the Pacific during the mid-Holocene are complex processes involving (1) changes in the quantity and 14C content of upwelled waters in tropical east Pacific (TEP) (frequency and intensity of ocean upwelling in the TEP, and contribution of Subantarctic Mode Water to the upwelled waters, which is influenced by the intensity and position of southern westerly winds), and (2) variations in ocean circulation associated with climate change (La Niña/El Niño conditions, intensity of easterly trade winds, positions of the Intertropical Convergence Zone and the South Pacific Convergence Zone), which control the spreading of the older upwelled surface waters in the TEP to the western sites. Our results imply the need for employing temporal changes in ΔR values, instead of constant (modern) values, for age calibration of Holocene marine samples not only for the SW Pacific sites but also for other tropical and subtropical sites in the Pacific.
•New ΔR values for SW Pacific for 0–8 ka based on 14C analysis of 230Th-dated corals.•Large ΔR variability across the Pacific, including the SW sites, for ∼5.4–8 ka.•Synchronous ΔR variations indicate large scale climate and ocean circulation drivers.•Urgent need for using temporal ΔR changes for improved 14C dating of marine samples.
We employ high-throughput thermal-neutron tomographic imaging to visualise internal diagnostic features of dense fossiliferous breccia from three Pleistocene cave localities in Sumatra, Indonesia. We ...demonstrate that these seemingly homogeneous breccias are an excellent source of data to aid in determining taphonomic and depositional histories of complex depositional sites such as tropical caves. X-ray Computed Tomographic (CT) imaging is gaining importance amongst palaeontologists as a non-destructive approach to studying fossil remains. Traditional methods of fossil preparation risk damage to the specimen and may destroy contextual evidence in the surrounding matrix. CT imaging can reveal the internal composition and structure of fossils contained within consolidated sediment/rock matrices prior to any destructive mechanical or chemical preparation. Neutron computed tomography (NCT) provides an alternative contrast to X-rays, and in some circumstances, is capable of discerning denser matrices impenetrable to or yielding no contrast with CT imaging. High-throughput neutron imaging reduces neutron fluence during scanning which means there is less residual neutron-induced radioactivation in geological samples; allowing for earlier subsequent analyses. However, this approach remains unutilised in palaeontology, archaeology or geological surveys. Results suggest that the primary agents in the formation of the breccias and concentration of incorporated vertebrate remains are several rapid depositional phases of water and sediment gravity flow. This study highlights the potential for future analyses of breccia deposits in palaeontological studies in caves around the world.
BACKGROUNDUniversities face challenges in preparing future nurses for the workforce. It is essential to guide educators on strategies to achieve similar learning objectives to overcoming these ...challenges. Educators widely use the observer role in simulation, but researchers do not study the role thoroughly in current simulation research. There is a lack of discipline-specific research exploring how observers learn in simulation and if they can engage in the experiential learning intended in the simulation activity. OBJECTIVESThe objective of this research is to determine the difference in simulation effectiveness between the process-based role versus the response-based role (observers) in participants during simulation-based learning experiences. DESIGNThis research used a quasi-experimental posttest only design to determine differences in simulation effectiveness among learner roles using the Simulation Effectiveness Tool-Modified (SET-M). SETTING & PARTICIPANTSThe researcher collected data from 193 prelicensure nursing students enrolled in any semester of one Midwestern undergraduate baccalaureate nursing program. METHODSNursing students completed the assigned face-to-face simulations in their current curriculum plan. Each participant was randomly assigned to a participant role: direct participant role as either a primary or secondary nurse, non-directed observer with no briefing or observer guide, direct observer with an observation guide, or in-scenario observer assigned to a non-clinical or other professional role within the scenario. After debriefing of the simulation, participants completed the demographic survey and SET-M. RESULTSThere were no significant differences found in prelicensure nursing students' simulation effectiveness among the four participant roles studied. CONCLUSIONThis study suggests simulation effectiveness (learning and confidence) happens regardless of the participants role during the simulation activity. Educators should consider what roles are necessary within each scenario and assign observation roles as needed.
Data are conflicting regarding an association between treatment of acute COVID-19 with nirmatrelvir-ritonavir (N-R) and virologic rebound (VR).
To compare the frequency of VR in patients with and ...without N-R treatment for acute COVID-19.
Observational cohort study.
Multicenter health care system in Boston, Massachusetts.
Ambulatory adults with acute COVID-19 with and without use of N-R.
Receipt of 5 days of N-R treatment versus no COVID-19 therapy.
The primary outcome was VR, defined as either a positive SARS-CoV-2 viral culture result after a prior negative result or 2 consecutive viral loads above 4.0 log
copies/mL that were also at least 1.0 log
copies/mL higher than a prior viral load below 4.0 log
copies/mL.
Compared with untreated persons (
= 55), those taking N-R (
= 72) were older, received more COVID-19 vaccinations, and more commonly had immunosuppression. Fifteen participants (20.8%) taking N-R had VR versus 1 (1.8%) who was untreated (absolute difference, 19.0 percentage points 95% CI, 9.0 to 29.0 percentage points;
= 0.001). All persons with VR had a positive viral culture result after a prior negative result. In multivariable models, only N-R use was associated with VR (adjusted odds ratio, 10.02 CI, 1.13 to 88.74;
= 0.038). Virologic rebound was more common among those who started therapy within 2 days of symptom onset (26.3%) than among those who started 2 or more days after symptom onset (0%) (
= 0.030). Among participants receiving N-R, those who had VR had prolonged shedding of replication-competent virus compared with those who did not have VR (median, 14 vs. 3 days). Eight of 16 participants (50% CI, 25% to 75%) with VR also reported symptom rebound; 2 were completely asymptomatic. No post-VR resistance mutations were detected.
Observational study design with differences between the treated and untreated groups; positive viral culture result was used as a surrogate marker for risk for ongoing viral transmission.
Virologic rebound occurred in approximately 1 in 5 people taking N-R, often without symptom rebound, and was associated with shedding of replication-competent virus.
National Institutes of Health.
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