The non-coding RNA subunit of telomerase provides the template for telomerase activity. In diverse fungi, 3′ end processing of telomerase RNA involves a single cleavage by the spliceosome. Here, we ...examine how human telomerase RNA (hTR) primary transcripts are processed into the mature form of precisely 451 nt. We find that the splicing inhibitor isoginkgetin mimics the effects of RNA exosome inhibition and causes accumulation of long hTR transcripts. Depletion of exosome components and accessory factors reveals functions for the cap binding complex (CBC) and the nuclear exosome targeting (NEXT) complex in hTR turnover. Whereas longer transcripts are predominantly degraded, shorter precursor RNAs are oligo-adenylated by TRF4-2 and either processed by poly(A)-specific ribonuclease (PARN) or degraded by the exosome. Our results reveal that hTR biogenesis involves a kinetic competition between RNA processing and degradation and suggest treatment options for telomerase insufficiency disorders.
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•CBC/NEXT recruits the exosome to 3′ extended forms of hTR•Precursor hTR RNAs are oligo-adenylated by TRF4-2•PARN competes with CBC/TRAMP/exosome-mediated degradation to generate mature hTR
Tseng et. al. find that 3′-extended human telomerase RNA (hTR) is predominantly degraded by the exosome in concert with accessory factors. In contrast, shorter precursor hTR RNAs are oligo-adenylated by TRF4-2 and either processed by poly(A)-specific ribonuclease (PARN) or degraded by the exosome.
CECL—an accounting response to lessons learned from the 2008 to 2009 financial crisis—like most accounting standards, is not perfect. Imperfections are a direct result of tradeoffs embedded in major ...new standards issued by the Financial Accounting Standards Board. Tradeoffs arise from cost—benefit judgments made over many years by individual Board members—often holding diverse views about costs and what constitutes decision-useful information. This article contributes to the assessment of those judgments and perceived weaknesses in CECL so that future Boards can continue the iterative process of improving U.S. GAAP. Some stakeholders assert that there are weaknesses because they believe CECL (a) will change how banks are managed; (b) may reduce the lending products provided; (c) necessitates a need for banks to raise capital; (d) would create widespread confusion among investors; and (e) could reduce the availability of credit. Now that CECL is effective for of the entire banking industry, the author believes the Financial Accounting Standards Board (FASB) and public policy-makers will benefit from rigorous academic research to help understand whether CECL met its main objective of providing more decision-useful information about expected credit losses. To achieve this objective, CECL strived to better align measurement of the allowance for credit losses (a valuation account) with changes in credit risk and to require consideration of a broader range of information. This article explores the relevant accounting issues and early financial reporting results to pique the interest of academic researchers.
is a common commensal and an opportunistic pathogen. Suspected pneumococcal upper respiratory infections and pneumonia are often treated with macrolide antibiotics. Macrolides are bacteriostatic ...antibiotics and inhibit protein synthesis by binding to the 50S ribosomal subunit. The widespread use of macrolides is associated with increased macrolide resistance in
, and the treatment of pneumococcal infections with macrolides may be associated with clinical failures. In
, macrolide resistance is due to ribosomal dimethylation by an enzyme encoded by
(B), efflux by a two-component efflux pump encoded by
(E)/
(
(D)) and, less commonly, mutations of the ribosomal target site of macrolides. A wide array of genetic elements have emerged that facilitate macrolide resistance in
; for example
(B) is found on Tn
, while the
(E)/
operon is carried on the 5.4- or 5.5-kb Mega element. The macrolide resistance determinants,
(B) and
(E)/
, are also found on large composite Tn
-like elements most notably Tn
, Tn
, and Tn
. Introductions of 7-valent and 13-valent pneumococcal conjugate vaccines (PCV-7 and PCV-13) have decreased the incidence of macrolide-resistant invasive pneumococcal disease, but serotype replacement and emergence of macrolide resistance remain an important concern.
Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and ...the development of reading, written language, and math learning disabilities (LD).
This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota, from 1976 to 1982 and who remained in the community at 5 yr of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, sex, and birth weight.
Of the 5,357 children in this cohort, 593 received general anesthesia before age 4 yr. Compared with those not receiving anesthesia (n = 4,764), a single exposure to anesthesia (n = 449) was not associated with an increased risk of LD (hazard ratio = 1.0; 95% confidence interval, 0.79-1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for LD (hazard ratio = 1.59; 95% confidence interval, 1.06-2.37, and hazard ratio = 2.60; 95% confidence interval, 1.60-4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P = 0.016).
Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. These data cannot reveal whether anesthesia itself may contribute to LD or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.
While the aurora has attracted attention for millennia, important questions remain unanswered. Foremost is how auroral electrons are accelerated before colliding with the ionosphere and producing ...auroral light. Powerful Alfvén waves are often found traveling Earthward above auroras with sufficient energy to generate auroras, but there has been no direct measurement of the processes by which Alfvén waves transfer their energy to auroral electrons. Here, we show laboratory measurements of the resonant transfer of energy from Alfvén waves to electrons under conditions relevant to the auroral zone. Experiments are performed by launching Alfvén waves and simultaneously recording the electron velocity distribution. Numerical simulations and analytical theory support that the measured energy transfer process produces accelerated electrons capable of reaching auroral energies. The experiments, theory, and simulations demonstrate a clear causal relationship between Alfvén waves and accelerated electrons that directly cause auroras.
We examined the risk for postoperative delirium (POD) in patients with mild cognitive impairment (MCI) or dementia, and the association between POD and subsequent development of MCI or dementia in ...cognitively normal elderly patients.
Patients ≥65 yr of age enrolled in the Mayo Clinic Study of Aging who were exposed to any type of anaesthesia from 2004 to 2014 were included. Cognitive status was evaluated before and after surgery by neuropsychological testing and clinical assessment, and was defined as normal or MCI/dementia. Postoperative delirium was detected with the Confusion Assessment Method for the intensive care unit. Logistic regression analyses were performed.
Among 2014 surgical patients, 74 (3.7%) developed POD. Before surgery, 1667 participants were cognitively normal, and 347 met MCI/dementia criteria. The frequency of POD was higher in patients with pre-existing MCI/dementia compared with no MCI/dementia {8.7 vs 2.6%; odds ratio (OR) 2.53, 95% confidence interval (CI) 1.52–4.21; P<0.001}. Postoperative delirium was associated with lower education OR, 3.40 (95% CI, 1.60–7.40); P=0.002 for those with <12 vs ≥16 yr of schooling. Of the 1667 patients cognitively normal at their most recent assessment, 1152 returned for postoperative evaluation, and 109 (9.5%) met MCI/dementia criteria. The frequency of MCI/dementia at the first postoperative evaluation was higher in patients who experienced POD compared with those who did not 33.3 vs 9.0%; adjusted OR, 3.00 (95% CI, 1.12–8.05); P=0.029.
Mild cognitive impairment or dementia is a risk for POD. Elderly patients who have not been diagnosed with MCI or dementia but experience POD are more likely to be diagnosed subsequently with MCI or dementia.
Migratory and rearing pathways of juvenile spring Chinook salmon (Oncorhynchus tshawytscha) were documented in the Willamette River basin to identify life histories and estimate their contribution to ...smolt production and population stability. We identified six primary life histories that included two phenotypes for early migratory tactics: fry that migrated up to 140–200 km shortly after emergence (movers) and fish that reared for 8–16 months in natal areas (stayers). Peak emigration of juvenile salmon from the Willamette River was in June–July (subyearling smolts), March–May (yearling smolts), and November–December (considered as “autumn smolts”). Alternative migratory behaviors of juvenile salmon were associated with extensive use of diverse habitats that eventually encompassed up to 400 rkm of the basin, including tributaries in natal areas and large rivers. Juvenile salmon that reared in natal reaches and migrated as yearlings were the most prevalent life history and had the lowest temporal variability. However, the total productivity of the basin was increased by the contribution of fish with dispersive life histories, which represented over 50% of the total smolt production. Life-history diversity reduced the variability in the total smolt population by 35% over the weighted mean of individual life histories, providing evidence of a considerable portfolio effect through the asynchronous contributions of life histories. Protecting and restoring a diverse suite of connected habitats in the Willamette River basin will promote the development and expression of juvenile life histories, thereby providing stability and resilience to native salmon populations.
Array tomography WACKER, I.; SCHROEDER, R.R.
Journal of microscopy (Oxford),
November 2013, Letnik:
252, Številka:
2
Journal Article
Recenzirano
Summary
In array tomography ordered, ribbon‐like assemblies of ultrathin serial sections are deposited on a solid substrate and imaged afterwards. The resulting images are then aligned and ...reconstructed into a three‐dimensional representation of the object. Depending on the preparation and labelling regime, different imaging modalities can be applied. When using light microscopy, the labelling with fluorescent markers would be the obvious choice, whereas the imaging in a scanning electron microscope would require impregnation with heavy metals. Depending on preparative constraints, the combination of diverse imaging modalities or truly correlative imaging is possible.
South Africa is in a critical power situation and is in dire need of additional generation capacity. Thus, renewable energy sources such as wind, solar and hydropower should be evaluated to identify ...highpotential and cost-effective sites. Rivers in South Africa, as a water-scarce country, are already heavily impounded, meaning that there are limited sites available for conventional hydropower generation. Instead, novel solutions such as retrofitting hydropower installations to existing infrastructure, like existing dams, are required. To estimate the retrofit hydropower potential at dams, a set of five tools was developed using Python 3, known as the University of Pretoria Retrofit Hydropower Evaluation Software (UP-RHES). The UP-RHES screens potential sites where historic flow records are available, then downloads the required flow records from the national database and performs a first-order hydraulic assessment of the site, as well as a first-order life cycle cost analysis. By applying the UP-RHES to 118 dams operated by the Department of Water and Sanitation (DWS), it was found that a total estimated hydropower potential of 128 MW with an annual energy output of between 385 and 469 GWh exists at South African dams. The Vaal, Pongolapoort, Goedertrouw and Blyderivierpoort Dams were found to be feasible sites with a combined capacity of 77 GWh/annum.
Healthcare utilization decreased during the COVID-19 pandemic, likely due to reduced transmission of infections and healthcare avoidance. Though various investigations have described these changing ...patterns in children, most have analyzed specific care settings. We compared healthcare utilization, prescriptions, and diagnosis patterns in children across the care continuum during the first year of the pandemic with preceding years. Using national claims data, we compared enrollees under 18 years during the pre-pandemic (January 2016 -mid-March 2020) and pandemic (mid-March 2020 through March 2021) periods. The pandemic was further divided into early (mid-March through mid-June 2020) and middle (mid-June 2020 through March 2021) periods. Utilization was compared using interrupted time series. The mean number of pediatric enrollees/month was 2,519,755 in the pre-pandemic and 2,428,912 in the pandemic period. Utilization decreased across all settings in the early pandemic, with the greatest decrease (76.9%, 95% confidence interval CI 72.6-80.5%) seen for urgent care visits. Only well visits returned to pre-pandemic rates during the mid-pandemic. Hospitalizations decreased by 43% (95% CI 37.4-48.1) during the early pandemic and were still 26.6% (17.7-34.6) lower mid-pandemic. However, hospitalizations in non-psychiatric facilities for various mental health disorders increased substantially mid-pandemic. Healthcare utilization in children dropped substantially during the first year of the pandemic, with a shift away from infectious diseases and a spike in mental health hospitalizations. These findings are important to characterize as we monitor the health of children, can be used to inform healthcare strategies during subsequent COVID-19 surges and/or future pandemics, and may help identify training gaps for pediatric trainees. Subsequent investigations should examine how changes in healthcare utilization impacted the incidence and outcomes of specific diseases.
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