Solid lipid nanoparticles of cholesteryl butyrate inhibit the proliferation of cancer cells in vitro and in vivo models.

BACKGROUND AND PURPOSE: Solid lipid nanoparticles containing cholesteryl butyrate (cholbut SLN) can be a delivery system for the anti-cancer drug butyrate. These nanoparticles inhibit adhesion of polymorphonuclear and tumour cells to endothelial cells and migration of tumour cells, suggesting that they may act as anti-inflammatory and anti-tumour agents. Here we have evaluated the effects of cholbut SLN on tumour cell growth using in vitro and in vivo models. EXPERIMENTAL APPROACH: Cholbut SLNs were incubated with cultures of four tumour cell lines, and cell growth was analysed by assessing viability, clonogenic capacity and cell cycle. Effects on intracellular signalling was assessed by Western blot analysis of Akt expression. The in vivo anti-tumour activity was measured in two models of PC-3 cell xenografts in SCID/Beige mice. KEY RESULTS: Cholbut SLN inhibited tumour cell line viability, clonogenic activity, Akt phosphorylation and cell cycle progression. In mice injected i.v. with PC3-Luc cells and treated with cholbut SLN, . in vivo optical imaging and histological analysis showed no metastases in the lungs of the treated mice. In another set of mice injected s.c. with PC-3 cells and treated with cholbut SLN when the tumour diameter reached 2 mm, analysis of the tumour dimensions showed that treatment with cholbut SLN substantially delayed tumour growth. CONCLUSION AND IMPLICATIONS: Cholbut SLN were effective in inhibiting tumour growth in vitro and in vivo. These effects may involve, in part, inhibition of Akt phosphorylation, which adds another mechanism to the activity of this multipotent drug

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Data from: Context-dependency of top-down, bottom-up, and density-dependent influences on cheetah demography

1. Research on drivers of demographic rates has mostly focused on top predators and their prey, and comparatively less research has considered the drivers of mesopredator demography. Of those limited studies, most focused on top-down effects of apex predators on mesopredator population dynamics, whereas studies investigating alternative mechanisms are less common. 2. In this study, we tested hypotheses related to top-down, bottom-up, and density-dependent regulation of demographic rates in an imperiled mesopredator, the cheetah (Acinonyx jubatus). 3. We used a 25-year dataset of lion density, cheetah density, and prey density from the Mun-Ya-Wana Conservancy in South Africa and assessed the effects of top-down, bottom-up, and density-dependent drivers on cheetah survival and reproduction. 4. In contrast to the top-down and bottom-up predications, both adult and juvenile cheetahs experienced the lowest survival during months with high prey densities and low lion densities. We only observed support for a density-dependent response in juvenile cheetahs, where they had a higher probability of reaching independence during times with low cheetah density, and low prey density. We did not identify any strong drivers of litter size. 5. Collectively, our results indicate that high apex predator abundance might not always have negative effects on mesopredator populations, and suggest that context dependency in top-down, bottom-up, and density-dependent factors may regulate demographic rates of cheetahs and other mesopredators. Our results highlight the complexities of population-level drivers of cheetah demographic rates and the importance of considering multiple hypotheses of mesopredator population regulation

Caution is warranted when using animal space-use and movement to infer behavioral states

Abstract Background Identifying the behavioral state for wild animals that can’t be directly observed is of growing interest to the ecological community. Advances in telemetry technology and statistical methodologies allow researchers to use space-use and movement metrics to infer the underlying, latent, behavioral state of an animal without direct observations. For example, researchers studying ungulate ecology have started using these methods to quantify behaviors related to mating strategies. However, little work has been done to determine if assumed behaviors inferred from movement and space-use patterns correspond to actual behaviors of individuals. Methods Using a dataset with male and female white-tailed deer location data, we evaluated the ability of these two methods to correctly identify male-female interaction events (MFIEs). We identified MFIEs using the proximity of their locations in space as indicators of when mating could have occurred. We then tested the ability of utilization distributions (UDs) and hidden Markov models (HMMs) rendered with single sex location data to identify these events. Results For white-tailed deer, male and female space-use and movement behavior did not vary consistently when with a potential mate. There was no evidence that a probability contour threshold based on UD volume applied to an individual’s UD could be used to identify MFIEs. Additionally, HMMs were unable to identify MFIEs, as single MFIEs were often split across multiple states and the primary state of each MFIE was not consistent across events. Conclusions Caution is warranted when interpreting behavioral insights rendered from statistical models applied to location data, particularly when there is no form of validation data. For these models to detect latent behaviors, the individual needs to exhibit a consistently different type of space-use and movement when engaged in the behavior. Unvalidated assumptions about that relationship may lead to incorrect inference about mating strategies or other behaviors

Incorporating human dimensions is associated with better wildlife translocation outcomes.

Wildlife translocations are increasingly used to combat declining biodiversity worldwide. Successful translocation often hinges on coexistence between humans and wildlife, yet not all translocation efforts explicitly include human dimensions (e.g., economic incentives, education programs, and conflict reduction assistance). To evaluate the prevalence and associated outcomes of including human dimensions as objectives when planning translocations, we analyze 305 case studies from the IUCN's Global Re-Introduction Perspectives Series. We find that fewer than half of all projects included human dimension objectives (42%), but that projects including human dimension objectives were associated with improved wildlife population outcomes (i.e., higher probability of survival, reproduction, or population growth). Translocation efforts were more likely to include human dimension objectives if they involved mammals, species with a history of local human conflict, and local stakeholders. Our findings underscore the importance of incorporating objectives related to human dimensions in translocation planning efforts to improve conservation success

Latitudinal variation in snowshoe hare (Lepus americanus) body mass: A test of Bergmann’s Rule

The relationship between body size and latitude has been the focus of dozens of studies across many species. However, results of testing Bergmann’s Rule – that organisms in colder climates or at higher latitudes possess larger body sizes – have been inconsistent across studies. We investigated whether snowshoe hares (Lepus americanus Erxleben, 1777) follow the Rule by investigating differences in body mass using data from six published studies and from data of 755 individual hares captured from ten populations across North America covering 26° of latitude. We also explored alternative hypotheses related to variation in hare body mass, including winter severity, length of growing season, elevation, and snow depth. We found body mass of hares varied throughout their range, but the drivers of body mass differed based on geographic location. Females in northern populations followed Bergmann’s rule, whereas males did not. In northern populations male mass was related to average snow depth. In contrast, in southern populations body mass of both sexes was related to length of the growing season. These differences likely represent variation in the drivers of selection. Specifically, in the north, a large body size is beneficial to conserve heat because of low winter temperatures, whereas in the south, it is likely due to increased food supply associated with longer growing seasons.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Diverse migratory portfolios drive inter‐annual switching behavior of elk across the Greater Yellowstone Ecosystem

Abstract A growing body of evidence shows that some ungulates alternate between migratory and nonmigratory behaviors over time. Yet it remains unclear whether such short‐term behavioral changes can help explain reported declines in ungulate migration worldwide, as opposed to long‐term demographic changes. Furthermore, advances in tracking technology reveal that a simple distinction between migration and nonmigration may not sufficiently describe all individual behaviors. To better understand the dynamics and drivers of ungulate switching behavior, we investigated 14 years of movement data from 361 elk in 20 herds across the Greater Yellowstone Ecosystem (GYE). First, we categorized yearly individual behaviors using a clustering algorithm that identified similar migratory tactics across a continuum of behaviors. Then, we tested seven hypotheses to explain why some ungulates switch behaviors, and we evaluated how behavioral changes affected the proportions of different behaviors across the system. We identified four distinct behavioral tactics: residents (4.8% of elk‐years), short‐distance migrants (53.7%), elevational migrants (21.9%) and long‐distance migrants (19.6%). Of the 20 herds, 18 were partially migratory, and 5 had all four movement tactics present. We observed switches between migratory tactics in all sets of consecutive years during our study period, with an average of 22.5% of individual elk changing movement tactics from one year to the next. Elk in herds with higher movement tactic diversity were significantly more likely to switch tactics and often responded more effectively to adverse environmental conditions, compared to those in herds with low movement tactic diversity. During our study period, switching increased the prevalence of both short‐ and long‐distance migrants, decreased the prevalence of elevational migrants, and had no effect on the prevalence of residents. Our findings suggest that rather than contributing to the declining migratory behavior found in the GYE, switching behavior may enable greater resiliency to continuously changing environmental and anthropogenic conditions

Delaying surgery for patients with a previous SARS-CoV-2 infection

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Is perioperative COVID-19 really associated with worse surgical outcomes? A nationwide COVIDSurg propensity-matched analysis

BACKGROUND: Patients undergoing surgery with perioperative COVID-19 are suggested to have worse outcomes, but whether this is COVID-related or due to selection bias remains unclear. We aimed to compare the postoperative outcomes of patients with and without perioperative COVID-19. METHODS: Patients with perioperative COVID-19 diagnosed within 7 days before or 30 days after surgery between February and July 2020 from 68 US hospitals in COVIDSurg, an international multicenter database, were 1:1 propensity score matched to patients without COVID-19 undergoing similar procedures in the 2012 American College of Surgeons National Surgical Quality Improvement Program database. The matching criteria included demographics (e.g., age, sex), comorbidities (e.g., diabetes, chronic obstructive pulmonary disease, chronic kidney disease), and operation characteristics (e.g., type, urgency, complexity). The primary outcome was 30-day hospital mortality. Secondary outcomes included hospital length of stay and 13 postoperative complications (e.g., pneumonia, renal failure, surgical site infection). RESULTS: A total of 97,936 patients were included, 1,054 with and 96,882 without COVID-19. Prematching, COVID-19 patients more often underwent emergency surgery (76.1% vs. 10.3%, p < 0.001). A total of 843 COVID-19 and 843 non-COVID-19 patients were successfully matched based on demographics, comorbidities, and operative characteristics. Postmatching, COVID-19 patients had a higher mortality (12.0% vs. 8.1%, p = 0.007), longer length of stay (6 [2-15] vs. 5 [1-12] days), and higher rates of acute renal failure (19.3% vs. 3.0%, p < 0.001), sepsis (13.5% vs. 9.0%, p = 0.003), and septic shock (11.8% vs. 6.0%, p < 0.001). They also had higher rates of thromboembolic complications such as deep vein thrombosis (4.4% vs. 1.5%, p < 0.001) and pulmonary embolism (2.5% vs. 0.4%, p < 0.001) but lower rates of bleeding (11.6% vs. 26.1%, p < 0.001). CONCLUSION: Patients undergoing surgery with perioperative COVID-19 have higher rates of 30-day mortality and postoperative complications, especially thromboembolic, compared with similar patients without COVID-19 undergoing similar surgeries. Such information is crucial for the complex surgical decision making and counseling of these patients. (J Trauma Acute Care Surg. 2023;94: 513-524. Copyright (C) 2023 American Association for the Surgery of Trauma.)LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV