Adult neurogenesis in the olfactory epithelium is often depicted as a unidirectional pathway during homeostasis and repair. We challenge the unidirectionality of this model by showing that epithelial ...injury unlocks the potential for Ascl1+ progenitors and Neurog1+ specified neuronal precursors to dedifferentiate into multipotent stem/progenitor cells that contribute significantly to tissue regeneration in the murine olfactory epithelium (OE). We characterize these dedifferentiating cells using several lineage-tracing strains and single-cell mRNA-seq, and we show that Sox2 is required for initiating dedifferentiation and that inhibition of Ezh2 promotes multipotent progenitor expansion. These results suggest that the apparent hierarchy of neuronal differentiation is not irreversible and that lineage commitment can be overridden following severe tissue injury. We elucidate a previously unappreciated pathway for endogenous tissue repair by a highly regenerative neuroepithelium and introduce a system to study the mechanisms underlying plasticity in the OE that can be adapted for other tissues.
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•Injury unlocks multipotency of Ascl1+ and Neurog1+ neuronally specified progenitors•Induced multipotent progenitors transplant and maintain their multipotency•Single-cell RNA-seq reveals Ezh2 as an epigenetic regulator of multipotency•Sox2 is required for initiation of dedifferentiation, but not maintenance
Lin et al. demonstrate that Ascl1+ and Neurog1+ neuronal progenitors can acquire cell fate plasticity after injury using genetic lineage trace and transplantation assays. Injury-induced multipotency occurs through a developmentally reminiscent endogenous upregulation of Sox2, KLF4, and Pax6, and dedifferentiation efficiency can be enhanced by Ezh2 inhibition.
Climate change has exacerbated the occurrence of large‐scale sea surface temperature anomalies, or marine heatwaves (MHWs)—extreme phenomena often associated with mass mortality events of marine ...organisms. Using a combination of citizen science and federal data sets, we investigated the causal mechanisms of the 2014/2015 die‐off of Cassin's Auklets (Ptychoramphus aleuticus), a small zooplanktivorous seabird, during the NE Pacific MHW of 2013–2015. Carcass deposition followed an effective reduction in the energy content of mesozooplankton, coincident with the loss of cold‐water foraging habitat caused by the intrusion of the NE Pacific MHW into the nearshore environment. Models examining interannual variability in effort‐controlled carcass abundance (2001–2014) identified the biomass of lipid‐poor zooplankton as the dominant predictor of increased carcass abundance. In 2014, Cassin's Auklets dispersing from colonies in British Columbia likely congregated into a nearshore band of cooler upwelled water and ultimately died from starvation following the shift in zooplankton composition associated with onshore transport of the NE Pacific MHW. For Cassin's Auklets, already in decline due to ocean warming, large‐scale and persistent MHWs might represent a global population precipice.
Plain Language Summary
During the winter of 2014/2015, thousands of Cassin's Auklets, a small seabird that breeds in the NE Pacific, were found dead on beaches from California to British Columbia, Canada. We show that wide‐scale starvation was due to a change in food quality associated with warmer ocean temperatures preceding and during the die‐off. This research highlights that more frequent and intense ocean warming events may have complex impacts on food webs with population consequences for marine predators, particularly seabirds such as Cassin's Auklets.
Key Points
During the winter of 2014/2015, over 9,000 (>100 x normal) dead Cassin's Auklets were observed on beaches from California to British Columbia
The die‐off was ultimately caused by a reduction in zooplankton prey energy content as a result of the NE Pacific marine heatwave (MHW)
The NE Pacific MHW likely inflated event magnitude by compressing cold‐water habitat, and by proxy live birds, closer to shore than usual
Inaccurate determination of baseline kidney function can misclassify acute kidney injury (AKI) and affect the study of AKI-related outcomes. No consensus exists on how to optimally determine baseline ...kidney function when multiple preadmission creatinine measurements are available.
The accuracy of commonly used methods for estimating baseline serum creatinine was compared with that of a reference standard adjudicated by a panel of board-certified nephrologists in 379 patients with AKI or CKD admitted to a tertiary referral center.
Agreement between estimating methods and the reference standard was highest when using creatinine values measured 7-365 days before admission. During this interval, the intraclass correlation coefficient (ICC) for the mean outpatient serum creatinine level (0.91 95% confidence interval (CI), 0.88-0.92) was higher than the most recent outpatient (ICC, 0.84 95% CI, 0.80-0.88; P<0.001) and the nadir outpatient (ICC, 0.83 95% CI, 0.76-0.87; P<0.001) serum creatinine. Using the final creatinine value from a prior inpatient admission increased the ICC of the most recent outpatient creatinine method (0.88 95% CI, 0.85-0.91). Performance of all methods declined or was unchanged when the time interval was broadened to 2 years or included serum creatinine measured within a week of admission.
The mean outpatient serum creatinine measured within a year of hospitalization most closely approximates nephrologist-adjudicated serum creatinine values.
Recently, theory and research have supported psychological capital (PsyCap) as an emerging core construct linked to positive outcomes at the individual and organizational level. However, to date, ...little attention has been given to PsyCap development through training interventions; nor have there been attempts to determine empirically if such PsyCap development has a causal impact on participants' performance. To fill these gaps we first conducted a pilot test of the PsyCap intervention (PCI) model with a randomized control group design. Next, we conducted a follow‐up study with a cross section of practicing managers to determine if following the training guidelines of the PCI caused the participants' performance to improve. Results provide beginning empirical evidence that short training interventions such as PCI not only may be used to develop participants' psychological capital, but can also lead to an improvement in their on‐the‐job performance. The implications these findings have for human resource development and performance management conclude the article.
Evolution of metazoan morphological disparity Deline, Bradley; Greenwood, Jennifer M.; Clark, James W. ...
Proceedings of the National Academy of Sciences - PNAS,
09/2018, Letnik:
115, Številka:
38
Journal Article
Recenzirano
Odprti dostop
The animal kingdom exhibits a great diversity of organismal form (i.e., disparity). Whether the extremes of disparity were achieved early in animal evolutionary history or clades continually explore ...the limits of possible morphospace is subject to continuing debate. Here we show, through analysis of the disparity of the animal kingdom, that, even though many clades exhibit maximal initial disparity, arthropods, chordates, annelids, echinoderms, and mollusks have continued to explore and expand the limits of morphospace throughout the Phanerozoic, expanding dramatically the envelope of disparity occupied in the Cambrian. The “clumpiness” of morphospace occupation by living clades is a consequence of the extinction of phylogenetic intermediates, indicating that the original distribution of morphologies was more homogeneous. The morphological distances between phyla mirror differences in complexity, body size, and species-level diversity across the animal kingdom. Causal hypotheses of morphologic expansion include time since origination, increases in genome size, protein repertoire, gene family expansion, and gene regulation. We find a strong correlation between increasing morphological disparity, genome size, and microRNA repertoire, but no correlation to protein domain diversity. Our results are compatible with the view that the evolution of gene regulation has been influential in shaping metazoan disparity whereas the invasion of terrestrial ecospace appears to represent an additional gestalt, underpinning the post-Cambrian expansion of metazoan disparity.
Placental mammals comprise three principal clades: Afrotheria (e.g., elephants and tenrecs), Xenarthra (e.g., armadillos and sloths), and Boreoeutheria (all other placental mammals), the ...relationships among which are the subject of controversy and a touchstone for debate on the limits of phylogenetic inference. Previous analyses have found support for all three hypotheses, leading some to conclude that this phylogenetic problem might be impossible to resolve due to the compounded effects of incomplete lineage sorting (ILS) and a rapid radiation. Here we show, using a genome scale nucleotide data set, microRNAs, and the reanalysis of the three largest previously published amino acid data sets, that the root of Placentalia lies between Atlantogenata and Boreoeutheria. Although we found evidence for ILS in early placental evolution, we are able to reject previous conclusions that the placental root is a hard polytomy that cannot be resolved. Reanalyses of previous data sets recover Atlantogenata + Boreoeutheria and show that contradictory results are a consequence of poorly fitting evolutionary models; instead, when the evolutionary process is better-modeled, all data sets converge on Atlantogenata. Our Bayesian molecular clock analysis estimates that marsupials diverged from placentals 157-170 Ma, crown Placentalia diverged 86-100 Ma, and crown Atlantogenata diverged 84-97 Ma. Our results are compatible with placental diversification being driven by dispersal rather than vicariance mechanisms, postdating early phases in the protracted opening of the Atlantic Ocean.
Background Robotic technology is one of the most recent technological changes in coronary artery bypass graft (CABG) operations. The current analysis was conducted to identify trends in the use and ...outcomes of robotic-assisted CABG (RA-CABG). Methods A retrospective analysis was performed using data from The Society of Thoracic Surgeons Adult Cardiac Surgery Database between 2006 and 2012. Patient and site-level characteristics were compared between traditional CABG and RA-CABG. Operative death, postoperative length of stay, and postoperative complications were compared between the two groups. Results The number of sites using RA-CABG remained relatively constant during the study period (from 148 in 2006 to 151 in 2012). The volume of RA-CABG as a percentage of the total CABG procedures increased slightly from 0.59% (872 RA-CABG of 127,717 total CABG) in 2006 to 0.97% (1,260 RA-CABG of 97,249 total CABG) in 2012. The RA-CABG patients were significantly younger (64 vs 65 years, p < 0.0001), had fewer comorbidities, and had lower rates of cardiopulmonary bypass use (22.4% vs 80.4%, p < 0.0001). RA-CABG patients had significantly lower unadjusted major complication rates (10.2% vs 13.5%, p < 0.0001), including postoperative renal failure (2.2% vs 2.9%, p < 0.0001), and shorter length of stay (4 vs 5 days, p < 0.0001). The difference in operative death was not significant (odds ratio, 1.10; 95% confidence interval, 0.92 to 1.30, p = 0.29). Conclusions RA-CABG use remained relatively stagnant during the analysis period despite lower rates of major perioperative complications and no difference in operative deaths. Additional analysis is needed to fully understand the role that robotic technology will play in CABG operations in the future.
The aim of this study was to quantify time in therapeutic range (TTR) before and after a temporary interruption of warfarin due to an intervention in the Outcomes Registry for Better Informed ...Treatment of atrial fibrillation (AF). AF patients on warfarin who had a temporary interruption followed by resumption were identified. A nonparametric method for estimating survival functions for interval censored data was used to examine the first therapeutic International Normalized Ratio (INR) after interruption. TTR was compared using Wilcoxon signed rank test. Cox proportional hazards model was used to investigate the association between TTR in the first 3 months after interruption and subsequent outcomes at 3 to 9 months. Of 9,749 AF patients, 71% were on warfarin. Over a median (IQR) follow-up of 2.6 (1.8 to 3.1) y, 33% of patients had a total of 3,022 temporary interruptions. The first therapeutic INR was recorded within 1 week in 35.0% (95% confidence interval 32.6% to 37.4%), 2 weeks in 54.6% (52.2% to 57.0%), 30 days in 70.0% (67.9% to 72.1%) and 90 days in 91.3% (90.0% to 92.5%) of patients. Compared with pre-interruption, TTR 3 months after interruption was significantly lower (61.1% 36.6% to 85.0% vs 67.6% 50.0% to 81.3%, p <0.0001). A 10 unit increment in the TTR in the first 3 months after interruption was associated with a lower risk of major bleeding Hazard ratio 0.91 (0.85 to 0.97), p = 0.005. This association was noted in patients who received bridging anticoagulation, but not in those who did not. In conclusion, temporary interruption of warfarin is common, and nearly half of these patients had subtherapeutic INR after 2 weeks. Lower TTR in the first 3 months after interruption was associated with higher incidence of major bleeding in patients who received bridging anticoagulation.
Introduction
We investigated associations between neighborhood racial/ethnic segregation and cognitive change.
Methods
We used data (n = 1712) from the Multi‐Ethnic Study of Atherosclerosis. ...Racial/ethnic segregation was assessed using Getis‐Ord (Gi*) z‐scores based on American Community Survey Census tract data (higher Gi* = greater spatial clustering of participant's race/ethnicity). Global cognition and processing speed were assessed twice, 6 years apart. Adjusted multilevel linear regression tested associations between Gi* z‐scores and cognition. Effect modification by race/ethnicity, income, education, neighborhood socioeconomic status, and neighborhood social support was tested.
Results
Participants were on average 67 years old; 43% were White, 11% Chinese, 29% African American/Black, 17% Hispanic; 40% had high neighborhood segregation (Gi* > 1.96). African American/Black participants with greater neighborhood segregation had greater processing speed decline in stratified analyses, but no interactions were significant.
Discussion
Segregation was associated with greater processing speed declines among African American/Black participants. Additional follow‐ups and comprehensive cognitive batteries may further elucidate these findings.
Highlights
A study of neighborhood racial/ethnic segregation and change in cognition.
Study was based on a racially and geographically diverse, population‐based cohort of older adults.
Racial/ethnic segregation (clustering) was measured by the Getis‐ord (Gi*) statistic.
We saw faster processing speed decline among Black individuals in segregated neighborhoods.
Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. ...Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow-up data were included (N=9019). CKD was defined as an estimated creatinine clearance <60 mL /min. Patient characteristics were compared by CKD status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant ( OAC ) use and outcomes and antiarrhythmic drug use and outcomes stratified by CKD stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60 mL /min. Patients with CKD were older and had higher CHA
DS
VAS c and Anticoagulant and Risk Factors in Atrial Fibrillation (ATRIA) scores. A rhythm control strategy was selected less frequently in patients with CKD , while OAC use was lower among Stage IV and V CKD patients. After adjustment, no significant interaction was noted for OAC and CKD on all-cause mortality ( P=0.5442) or cardiovascular death ( P=0.1233), although a trend for increased major bleeding ( P=0.0608) and stroke, systemic embolism or transient ischemic attack ( P=0.0671) was observed. No interaction was noted for antiarrhythmic drug use and CKD status on all-cause mortality ( P=0.9706), or stroke, systemic embolism or transient ischemic attack ( P=0.4218). Conclusions Patients with atrial fibrillation and CKD are less likely to be treated with rhythm control. Patients with advanced CKD are less likely to receive OAC . Finally, outcomes with OAC in patients with advanced CKD may be materially different with higher rates of both bleeding and stroke.
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