•Polystyrene nanoparticles (PS NPs) crossed the zebrafish chorion.•PS NPs accumulated in numerous organs during development.•Bradycardia and hypoactivity were observed following exposure to PS NPs.
...Plastic pollution is a critical environmental concern and comprises the majority of anthropogenic debris in the ocean, including macro, micro, and likely nanoscale (less than 100nm in at least one dimension) plastic particles. While the toxicity of macroplastics and microplastics is relatively well studied, the toxicity of nanoplastics is largely uncharacterized. Here, fluorescent polystyrene nanoparticles (PS NPs) were used to investigate the potential toxicity of nanoplastics in developing zebrafish (Danio rerio), as well as to characterize the uptake and distribution of the particles within embryos and larvae. Zebrafish embryos at 6h post-fertilization (hpf) were exposed to PS NPs (0.1, 1, or 10ppm) until 120 hpf. Our results demonstrate that PS NPs accumulated in the yolk sac as early as 24 hpf and migrated to the gastrointestinal tract, gallbladder, liver, pancreas, heart, and brain throughout development (48–120 hpf). Accumulation of PS NPs decreased during the depuration phase (120–168 hpf) in all organs, but at a slower rate in the pancreas and gastrointestinal tract. Notably, exposure to PS NPs did not induce significant mortality, deformities, or changes to mitochondrial bioenergetics, but did decrease the heart rate. Lastly, exposure to PS NPs altered larval behavior as evidenced by swimming hypoactivity in exposed larvae. Taken together, these data suggest that at least some nanoplastics can penetrate the chorion of developing zebrafish, accumulate in the tissues, and affect physiology and behavior, potentially affecting organismal fitness in contaminated aquatic ecosystems.
Human disturbance can influence wildlife behaviour, which can have implications for wildlife populations. For example, wildlife may be more vigilant near human disturbance, resulting in decreased ...forage intake and reduced reproductive success. We measured the effects of human activities compared to predator and other environmental factors on the behaviour of elk (Cervus elaphus Linnaeus 1758) in a human-dominated landscape in Alberta, Canada.
We collected year-round behavioural data of elk across a range of human disturbances. We estimated linear mixed models of elk behaviour and found that human factors (land-use type, traffic and distance from roads) and elk herd size accounted for more than 80% of variability in elk vigilance. Elk decreased their feeding time when closer to roads, and road traffic volumes of at least 1 vehicle every 2 hours induced elk to switch into a more vigilant behavioural mode with a subsequent loss in feeding time. Other environmental factors, thought crucial in shaping vigilance behaviour in elk (natural predators, reproductive status of females), were not important. The highest levels of vigilance were recorded on public lands where hunting and motorized recreational activities were cumulative compared to the national park during summer, which had the lowest levels of vigilance.
In a human-dominated landscape, effects of human disturbance on elk behaviour exceed those of habitat and natural predators. Humans trigger increased vigilance and decreased foraging in elk. However, it is not just the number of people but also the type of human activity that influences elk behaviour (e.g. hiking vs. hunting). Quantifying the actual fitness costs of human disturbance remains a challenge in field studies but should be a primary focus for future researches. Some species are much more likely to be disturbed by humans than by non-human predators: for these species, quantifying human disturbance may be the highest priority for conservation.
The Albumin-Bilirubin score (ALBI) has been established to predict outcomes after hepatectomy. However, the relative value of ALBI and Model for End-Stage Liver Disease (MELD) in predicting ...post-hepatectomy liver failure and mortality has not been adequately evaluated. Therefore, the aim of this study was to validate and compare ALBI and MELD with respect to post-hepatectomy liver failure and mortality.
Patients undergoing major hepatectomy (≥3 segments) or partial hepatectomy (≤2 segments) were identified in the 2014 to 2017 American College of Surgeons NSQIP Procedure Targeted Participant Use File. Univariable and multivariable analyses were performed for 30-day post-hepatectomy liver failure (PHLF) and mortality. Predictive accuracy was assessed using a receiver operator characteristic curve and calculating the area under the curve (AUC).
For 13,783 patients, median ALBI was –2.6, and median MELD score was 6.9. Severe PHLF (grade B to C) and mortality rates were 2.9% and 1.8%, respectively. Multivariable analyses revealed ALBI grade 2/3 to be a stronger predictor than MELD ≥10 with respect to severe PHLF (odds ratio OR 2.30; 95% CI, 1.95 to 2.73; p < 0.001 vs OR 1.00; 95% CI, 0.78 to 1.23; p = 0.99) and mortality (OR 3.35; 95% CI, 2.49 to 4.52; p < 0.001 vs OR 1.73; 95% CI, 1.36 to 2.20; p < 0.001). ALBI also had better discrimination compared with MELD for severe PHLF (AUC 0.67 vs AUC 0.60) and mortality (AUC 0.70 vs AUC 0.58) in patients with hepatocellular carcinoma.
ALBI is a powerful predictor of PHLF and mortality. Compared with MELD, ALBI is more accurate, especially in patients with hepatocellular carcinoma.
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The intramolecular distribution of nitrogen isotopes in N₂O is an emerging tool for defining the relative importance of microbial sources of this greenhouse gas. The application of intramolecular ...isotopic distributions to evaluate the origins of N₂O, however, requires a foundation in laboratory experiments in which individual production pathways can be isolated. Here we evaluate the site preferences of N₂O produced during hydroxylamine oxidation by ammonia oxidizers and by a methanotroph, ammonia oxidation by a nitrifier, nitrite reduction during nitrifier denitrification, and nitrate and nitrite reduction by denitrifiers. The site preferences produced during hydroxylamine oxidation were 33.5 ± 1.2per mille, 32.5 ± 0.6per mille, and 35.6 ± 1.4per mille for Nitrosomonas europaea, Nitrosospira multiformis, and Methylosinus trichosporium, respectively, indicating similar site preferences for methane and ammonia oxidizers. The site preference of N₂O from ammonia oxidation by N. europaea (31.4 ± 4.2per mille) was similar to that produced during hydroxylamine oxidation (33.5 ± 1.2per mille) and distinct from that produced during nitrifier denitrification by N. multiformis (0.1 ± 1.7per mille), indicating that isotopomers differentiate between nitrification and nitrifier denitrification. The site preferences of N₂O produced during nitrite reduction by the denitrifiers Pseudomonas chlororaphis and Pseudomonas aureofaciens (-0.6 ± 1.9per mille and -0.5 ± 1.9per mille, respectively) were similar to those during nitrate reduction (-0.5 ± 1.9per mille and -0.5 ± 0.6per mille, respectively), indicating no influence of either substrate on site preference. Site preferences of approximately33per mille and approximately0per mille are characteristic of nitrification and denitrification, respectively, and provide a basis to quantitatively apportion N₂O.
Background The Fistula Risk Score (FRS) is a clinical tool developed from single-institutional data using primarily intraoperative factors to characterize the risk of clinically relevant pancreatic ...fistula (CR-POPF) after pancreaticoduodenectomy. We developed a modified FRS based on objective, nationally accrued data that is more readily determined before resection. Study Design The 2012 NSQIP Pancreatic Demonstration Project (PDP) was used to identify 1,731 pancreaticoduodenectomy resections over 14 months (2011 to 2012). A randomly generated 70% cohort was used for model development, and the remaining 30% for internal validation. Univariate analysis was used to identify predictors of CR-POPF. Variables with a value of p < 0.1 were included in multivariable modeling. Results Five significant predictors of CR-POPF were identified and assigned points based on odds ratios: sex, BMI, preoperative total bilirubin, pancreatic ductal diameter, and gland texture. The 10-point model was further applied to the 2014 PDP for external validation. In the testing group, risk scores of 0 to 2 (negligible risk), 3 to 6 (low risk), 7 to 8 (intermediate risk), and 9 to 10 (high risk) were associated with CR-POPF rates of 0%, 6.7%, 16.4%, and 33.7%, respectively. Similar values were seen using the internal validation cohort: 0%, 6.3%, 13.5%, and 31.0%, respectively. The external validation values were 2.9%, 10.2%, 16.4%, and 25.8%, respectively. Conclusions This modified FRS allows for estimation of CR-POPF risk using preoperative and easily determined intraoperative factors, and will allow comparison of performance data for individual surgeons to national norms, improved perioperative counseling, and potential for scrutinizing and/or implementing interventions designed to decrease CR-POPF rates.
Speech is produced over time, and this makes sensitivity to timing between speech events crucial for understanding language. Two experiments investigated whether perception of function words (e.g., ...or, are) is rate dependent in casual speech, which often contains phonetic segments that are spectrally quite reduced. In Experiment I, talkers spoke sentences containing a target function word; slowing talkers' speech rate around this word caused listeners to perceive sentences as lacking the word (e.g., leisure or time was perceived as leisure time). In Experiment 2, talkers spoke matched sentences lacking a function word; speeding talkers' speech rate around the region in which the function word had been embedded in Experiment I caused listeners to perceive a function word that was never spoken (e.g., leisure time was perceived as leisure or time). The results suggest that listeners formed expectancies based on speech rate, and these expectancies influenced the number of words and word boundaries perceived. These findings may help explain the robustness of speech recognition when speech signals are distorted (e.g., because of a casual speaking style).
The role of the microenvironment in T cell acute lymphoblastic leukemia (T-ALL), or any acute leukemia, is poorly understood. Here we demonstrate that T-ALL cells are in direct, stable contact with ...CXCL12-producing bone marrow stroma. Cxcl12 deletion from vascular endothelial, but not perivascular, cells impeded tumor growth, suggesting a vascular niche for T-ALL. Moreover, genetic targeting of Cxcr4 in murine T-ALL after disease onset led to rapid, sustained disease remission, and CXCR4 antagonism suppressed human T-ALL in primary xenografts. Loss of CXCR4 targeted key T-ALL regulators, including the MYC pathway, and decreased leukemia initiating cell activity in vivo. Our data identify a T-ALL niche and suggest targeting CXCL12/CXCR4 signaling as a powerful therapeutic approach for T-ALL.
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•T-ALL cells are in direct, stable contact with CXCL12-producing bone marrow stroma•Cxcl12 deletion in vascular endothelial, but not perivascular, cells suppresses disease•Cxcr4 deletion in T-ALL cells after disease onset inhibits leukemia progression•CXCR4 antagonism suppresses human T-ALL in a primary xenograft model
Pitt et al. identify a T cell acute lymphoblastic leukemia (T-ALL) niche and show that T-ALL cells are in direct, stable contact with CXCL12-producing bone marrow stroma. Importantly, targeting CXCL12 or its receptor CXCR4 expressed in T-ALL cells reduces tumor growth in murine T-ALL and xenograft models.
A major technological challenge in materials research is the large and complex parameter space, which hinders experimental throughput and ultimately slows down development and implementation. In ...single-walled carbon nanotube (CNT) synthesis, for instance, the poor yield obtained from conventional catalysts is a result of limited understanding of input-to-output correlations. Autonomous closed-loop experimentation combined with advances in machine learning (ML) is uniquely suited for high-throughput research. Among the ML algorithms available, Bayesian optimization (BO) is especially apt for exploration and optimization within such high-dimensional and complex parameter space. BO is an adaptive sequential design algorithm for finding the global optimum of a black-box objective function with the fewest possible measurements. Here, we demonstrate a promising application of BO in CNT synthesis as an efficient and robust algorithm which can (1) improve the growth rate of CNT in the BO-planner experiments over the seed experiments up to a factor 8; (2) rapidly improve its predictive power (or learning); (3) Consistently achieve good performance regardless of the number or origin of seed experiments; (4) exploit a high-dimensional, complex parameter space, and (5) achieve the former 4 tasks in just over 100 hundred experiments (~8 experimental hours) - a factor of 5× faster than our previously reported results.
Saccharomyces cerevisiae is an important unicellular yeast species within the biotechnological and the food and beverage industries. A significant application of this species is the production of ...ethanol, where concentrations are limited by cellular toxicity, often at the level of the cell membrane. Here, we characterize 61 S. cerevisiae strains for ethanol tolerance and further analyze five representatives with various ethanol tolerances. The most tolerant strain, AJ4, was dominant in coculture at 0 and 10% ethanol. Unexpectedly, although it does not have the highest noninhibitory concentration or MIC, MY29 was the dominant strain in coculture at 6% ethanol, which may be linked to differences in its basal lipidome. Although relatively few lipidomic differences were observed between strains, a significantly higher phosphatidylethanolamine concentration was observed in the least tolerant strain, MY26, at 0 and 6% ethanol compared to the other strains that became more similar at 10%, indicating potential involvement of this lipid with ethanol sensitivity. Our findings reveal that AJ4 is best able to adapt its membrane to become more fluid in the presence of ethanol and that lipid extracts from AJ4 also form the most permeable membranes. Furthermore, MY26 is least able to modulate fluidity in response to ethanol, and membranes formed from extracted lipids are least leaky at physiological ethanol concentrations. Overall, these results reveal a potential mechanism of ethanol tolerance and suggest a limited set of membrane compositions that diverse yeast species use to achieve this.
Many microbial processes are not implemented at the industrial level because the product yield is poorer and more expensive than can be achieved by chemical synthesis. It is well established that microbes show stress responses during bioprocessing, and one reason for poor product output from cell factories is production conditions that are ultimately toxic to the cells. During fermentative processes, yeast cells encounter culture media with a high sugar content, which is later transformed into high ethanol concentrations. Thus, ethanol toxicity is one of the major stresses in traditional and more recent biotechnological processes. We have performed a multilayer phenotypic and lipidomic characterization of a large number of industrial and environmental strains of
to identify key resistant and nonresistant isolates for future applications.
Jellyfish (Cnidaria, Scyphozoa) blooms appear to be increasing in both intensity and frequency in many coastal areas worldwide, due to multiple hypothesized anthropogenic stressors. Here, we propose ...that the proliferation of artificial structures - associated with (1) the exponential growth in shipping, aquaculture, and other coastal industries, and (2) coastal protection (collectively, "ocean sprawl") - provides habitat for jellyfish polyps and may be an important driver of the global increase in jellyfish blooms. However, the habitat of the benthic polyps that commonly result in coastal jellyfish blooms has remained elusive, limiting our understanding of the drivers of these blooms. Support for the hypothesized role of ocean sprawl in promoting jellyfish blooms is provided by observations and experimental evidence demonstrating that jellyfish larvae settle in large numbers on artificial structures in coastal waters and develop into dense concentrations of jellyfish-producing polyps.
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