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Abstract The neuropeptide substance-P (SP) is expressed from the TAC1 gene in sensory neurones where it acts as a key modulator of neurogenic inflammation. The promoter of TAC1 (TAC1prom) plays a central role in the regulation of the TAC1 gene but requires the presence of a second regulatory element; ECR2, to support TAC1 expression in sensory neurones and to respond appropriately to signalling pathways such as MAPkinases and noxious induction by capsaicin. We examined whether the effect of capsaicin on ECR2-TAC1prom activity in larger diameter neurones was cell autonomous or non- cell autonomous. We demonstrate that TRPV1 is not expressed in all the same cells as SP following capsaicin induction suggesting the presence of a non-cell autonomous mechanism for TAC1 up-regulation following capsaicin induction. In addition, we demonstrate that induction of SP and ECR1-TAC1prom activity in these larger diameter neurones can be induced by potassium depolarisation suggesting that, in addition to capsaicin induction, transgene activity may be modulated by voltage gated calcium channels. Furthermore, we show that NK1 is expressed in all SP- expressing cells after capsaicin induction and that an agonist of NK1 can activate both SP and the transgene in larger diameter neurones. These observations suggest the presence of an autocrine loop that controls the expression of the TAC1 promoter in sensory neurones. In contrast, induction of the TAC1 promoter by LPS was not dependent on ECR2 and did not occur in large diameter neurones. These studies demonstrate the diversity of mechanisms modulating the activity of the TAC1 promoter and provide novel directions for the development of new anti-inflammatory therapies.

Abstract Background Human genetic variation produces the wide range of phenotypic differences that make us individual. However, little is known about the distribution of variation in the most conserved functional regions of the human genome. We examined whether different subsets of the conserved human genome have been subjected to similar levels of selective constraint within the human population. We used set theory and high performance computing to carry out an analysis of the density of Single Nucleotide Polymorphisms (SNPs) within the evolutionary conserved human genome, at three different selective stringencies, intersected with exonic, intronic and intergenic coordinates. Results We demonstrate that SNP density across the genome is significantly reduced in conserved human sequences. Unexpectedly, we further demonstrate that, despite being conserved to the same degree, SNP density differs significantly between conserved subsets. Thus, both the conserved exonic and intronic genomes contain a significantly reduced density of SNPs compared to the conserved intergenic component. Furthermore the intronic and exonic subsets contain almost identical densities of SNPs indicating that they have been constrained to the same degree. Conclusion Our findings suggest the presence of a selective linkage between the exonic and intronic subsets and ascribes increased significance to the role of introns in human health. In addition, the identification of increased plasticity within the conserved intergenic subset suggests an important role for this subset in the adaptation and diversification of the human population.

The sole unifying feature of the incredibly diverse Archaea is their isoprenoid-based ether-linked lipid membranes. Unique lipid membrane composition, including an abundance of membrane-spanning tetraether lipids, impart resistance to extreme conditions. Many questions remain, however, regarding the synthesis and modification of tetraether lipids and how dynamic changes to archaeal lipid membrane composition support hyperthermophily. Tetraether membranes, termed glycerol dibiphytanyl glycerol tetraethers (GDGTs), are generated by tetraether synthase (Tes) by joining the tails of two bilayer lipids known as archaeol. GDGTs are often further specialized through the addition of cyclopentane rings by GDGT ring synthase (Grs). A positive correlation between relative GDGT abundance and entry into stationary phase growth has been observed, but the physiological impact of inhibiting GDGT synthesis has not previously been reported. Here, we demonstrate that the model hyperthermophile Thermococcus kodakarensis remains viable when Tes (TK2145) or Grs (TK0167) are deleted, permitting phenotypic and lipid analyses at different temperatures. The absence of cyclopentane rings in GDGTs does not impact growth in T. kodakarensis, but an overabundance of rings due to ectopic Grs expression is highly fitness negative at supra-optimal temperatures. In contrast, deletion of Tes resulted in the loss of all GDGTs, cyclization of archaeol, and loss of viability upon transition to the stationary phase in this model archaea. These results demonstrate the critical roles of highly specialized, dynamic, isoprenoid-based lipid membranes for archaeal survival at high temperatures., (© 2024 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.

We describe six datasets that contain GPS and accelerometer data of 202 Eurasian oystercatchers ( Haematopusostralegus ) spanning the period 2008-2021. Birds were equipped with GPS trackers in breeding and wintering areas in the Netherlands and Belgium. We used GPS trackers from the University of Amsterdam Bird Tracking System (UvA-BiTS) for several study purposes, including the study of space use during the breeding season, habitat use and foraging behaviour in the winter season, and impacts of human disturbance. To enable broader usage, all data have now been made open access. Combined, the datasets contain 6.0 million GPS positions, 164 million acceleration measurements and 7.0 million classified behaviour events (i.e., flying, walking, foraging, preening, and inactive). The datasets are deposited on the research repository Zenodo, but are also accessible on Movebank and as down-sampled occurrence datasets on the Global Biodiversity Information Facility (GBIF) and Ocean Biodiversity Information System (OBIS)., (Henk-Jan van der Kolk, Peter Desmet, Kees Oosterbeek, Andrew M. Allen, Martin J. Baptist, Roeland A. Bom, Sarah C. Davidson, Jan de Jong, Hans de Kroon, Bert Dijkstra, Rinus Dillerop, Adriaan M. Dokter, Magali Frauendorf, Tanja Milotić, Eldar Rakhimberdiev, Judy Shamoun-Baranes, Geert Spanoghe, Martijn van de Pol, Gunther Van Ryckegem, Joost Vanoverbeke, Eelke Jongejans, Bruno J. Ens.)

Background: Bio-logging and animal tracking datasets continuously grow in volume and complexity, documenting animal behaviour and ecology in unprecedented extent and detail, but greatly increasing the challenge of extracting knowledge from the data obtained. A large variety of analysis methods are being developed, many of which in effect are inaccessible to potential users, because they remain unpublished, depend on proprietary software or require significant coding skills., Results: We developed MoveApps, an open analysis platform for animal tracking data, to make sophisticated analytical tools accessible to a global community of movement ecologists and wildlife managers. As part of the Movebank ecosystem, MoveApps allows users to design and share workflows composed of analysis modules (Apps) that access and analyse tracking data. Users browse Apps, build workflows, customise parameters, execute analyses and access results through an intuitive web-based interface. Apps, coded in R or other programming languages, have been developed by the MoveApps team and can be contributed by anyone developing analysis code. They become available to all user of the platform. To allow long-term and cross-system reproducibility, Apps have public source code and are compiled and run in Docker containers that form the basis of a serverless cloud computing system. To support reproducible science and help contributors document and benefit from their efforts, workflows of Apps can be shared, published and archived with DOIs in the Movebank Data Repository. The platform was beta launched in spring 2021 and currently contains 49 Apps that are used by 316 registered users. We illustrate its use through two workflows that (1) provide a daily report on active tag deployments and (2) segment and map migratory movements., Conclusions: The MoveApps platform is meant to empower the community to supply, exchange and use analysis code in an intuitive environment that allows fast and traceable results and feedback. By bringing together analytical experts developing movement analysis methods and code with those in need of tools to explore, answer questions and inform decisions based on data they collect, we intend to increase the pace of knowledge generation and integration to match the huge growth rate in bio-logging data acquisition., (© 2022. The Author(s).)

The Arctic is entering a new ecological state, with alarming consequences for humanity. Animal-borne sensors offer a window into these changes. Although substantial animal tracking data from the Arctic and subarctic exist, most are difficult to discover and access. Here, we present the new Arctic Animal Movement Archive (AAMA), a growing collection of more than 200 standardized terrestrial and marine animal tracking studies from 1991 to the present. The AAMA supports public data discovery, preserves fundamental baseline data for the future, and facilitates efficient, collaborative data analysis. With AAMA-based case studies, we document climatic influences on the migration phenology of eagles, geographic differences in the adaptive response of caribou reproductive phenology to climate change, and species-specific changes in terrestrial mammal movement rates in response to increasing temperature., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Light-level geolocator tags use ambient light recordings to estimate the whereabouts of an individual over the time it carried the device. Over the past decade, these tags have emerged as an important tool and have been used extensively for tracking animal migrations, most commonly small birds. Analysing geolocator data can be daunting to new and experienced scientists alike. Over the past decades, several methods with fundamental differences in the analytical approach have been developed to cope with the various caveats and the often complicated data. Here, we explain the concepts behind the analyses of geolocator data and provide a practical guide for the common steps encompassing most analyses - annotation of twilights, calibration, estimating and refining locations, and extraction of movement patterns - describing good practices and common pitfalls for each step. We discuss criteria for deciding whether or not geolocators can answer proposed research questions, provide guidance in choosing an appropriate analysis method and introduce key features of the newest open-source analysis tools. We provide advice for how to interpret and report results, highlighting parameters that should be reported in publications and included in data archiving. Finally, we introduce a comprehensive supplementary online manual that applies the concepts to several datasets, demonstrates the use of open-source analysis tools with step-by-step instructions and code and details our recommendations for interpreting, reporting and archiving., (© 2019 The Authors. Journal of Animal Ecology © 2019 British Ecological Society.)

Treatment of homoallylic N-tosyl amines or allylic N-tosyl hydroxylamines with 1.5 equiv of a malonoyl peroxide provides a stereoselective method to access functionalized pyrrolidines and isoxazolidines. This metal free alkene oxyamination proceeds in 50-85% yield and up to 13:1 trans-selectivity. In addition, the relative stereochemistry of the oxygen and nitrogen substituents can be inverted through an oxidation/reduction sequence or inverting the stereochemistry of the starting alkene. Mechanistic investigations show a higher reactivity for hydroxyl nucleophiles over sulfonamide nucleophiles revealing a preference for dioxygenation over oxyamination.

Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission., (Copyright © 2018, The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Variation in the reactivity of the endocrine stress axis is thought to underlie aspects of persistent individual differences in behavior (i.e. animal personality). Previous studies, however, have focused largely on estimating baseline or peak levels of glucocorticoids (CORT), often in captive animals. In contrast, the temporal dynamics of the HPA axis-how quickly it turns on and off, for example-may better indicate how an individual copes with stressors. Moreover, these HPA components might be correlated, thereby representing endocrine suites. Using wild-caught great tits (Parus major) we tested birds for exploratory behavior using a standardized novel environment assay that serves as a validated proxy for personality. We then re-captured a subset of these birds (n=85) and characterized four components of HPA physiology: baseline, endogenous stress response, a dexamethasone (DEX) challenge to estimate the strength of negative feedback, and an adrenocorticotropic hormone (ACTH) challenge to estimate adrenal capacity. We predicted that these four HPA responses would be positively correlated and that less exploratory birds would have a more rapid onset of the stress response (a CORT elevation during the baseline bleed) and weaker negative feedback (higher CORT after DEX). We found support for the first two predictions but not the third. All four components were positively correlated with each other and less exploratory birds exhibited an elevation in CORT during the baseline bleed (<3min from capture). Less exploratory birds, however, did not exhibit weaker negative feedback following the DEX challenge, but did exhibit weaker adrenal capacity. Together, our findings provide partial support for the hypothesis that the temporal reactivity of the HPA axis is linked with consistent individual differences in behavior, with more cautious (slower exploring) individuals exhibiting a faster CORT response., (Copyright © 2017 Elsevier Inc. All rights reserved.)

S-acylation is a major posttranslational modification, catalyzed by the zinc finger DHHC domain containing (zDHHC) enzyme family. S-acylated proteins can be modified by different fatty acids; however, very little is known about how zDHHC enzymes contribute to acyl chain heterogeneity. Here, we used fatty acid-azide/alkyne labeling of mammalian cells, showing their transformation into acyl-CoAs and subsequent click chemistry-based detection, to demonstrate that zDHHC enzymes have marked differences in their fatty acid selectivity. This difference in selectivity was apparent even for highly related enzymes, such as zDHHC3 and zDHHC7, which displayed a marked difference in their ability to use C18:0 acyl-CoA as a substrate. Furthermore, we identified isoleucine-182 in transmembrane domain 3 of zDHHC3 as a key determinant in limiting the use of longer chain acyl-CoAs by this enzyme. This study uncovered differences in the fatty acid selectivity profiles of cellular zDHHC enzymes and mapped molecular determinants governing this selectivity.

Malonoyl peroxide 1, prepared in a single step from the commercially available diacid, is an effective reagent for the anti-dihydroxylation of alkenes. Reaction of 1 with an alkene in the presence of acetic acid at 40 °C followed by alkaline hydrolysis leads to the corresponding diol (35-92%) with up to 13:1 anti-selectivity. A mechanism consistent with experimental findings is proposed that accounts for the selectivity observed.

The large increase in the number of RN-to-BSN programs has occurred in the context of the expansion of Internet-based resources. This article expands on an earlier reported evaluation of a program based on community-derived needs. Several dimensions were identified that appear to contribute to student success in a blended-hybrid and completely online curricula. Students move through a synchronous cohort curriculum. The graduation rate for both programs was above the national average for all programs (80%), and graduation rate for the blended-hybrid program (92%) exceeded the online program (88%). Social support theory framed the important factors in a way that paralleled the factors reported by students as leading to their success., (Copyright 2014, SLACK Incorporated.)

Variation is key to the adaptability of species and their ability to survive changes to the Earth's climate and habitats. Plasticity in movement strategies allows a species to better track spatial dynamics of habitat quality. We describe the mechanisms that shape the movement of a long-distance migrant bird (turkey vulture, Cathartes aura) across two continents using satellite tracking coupled with remote-sensing science. Using nearly 10 years of data from 24 satellite-tracked vultures in four distinct populations, we describe an enormous amount of variation in their movement patterns. We related vulture movement to environmental conditions and found important correlations explaining how far they need to move to find food (indexed by the Normalized Difference Vegetation Index) and how fast they can move based on the prevalence of thermals and temperature. We conclude that the extensive variability in the movement ecology of turkey vultures, facilitated by their energetically efficient thermal soaring, suggests that this species is likely to do well across periods of modest climate change. The large scale and sample sizes needed for such analysis in a widespread migrant emphasizes the need for integrated and collaborative efforts to obtain tracking data and for policies, tools and open datasets to encourage such collaborations and data sharing.

Background: The movement of animals is strongly influenced by external factors in their surrounding environment such as weather, habitat types, and human land use. With advances in positioning and sensor technologies, it is now possible to capture animal locations at high spatial and temporal granularities. Likewise, scientists have an increasing access to large volumes of environmental data. Environmental data are heterogeneous in source and format, and are usually obtained at different spatiotemporal scales than movement data. Indeed, there remain scientific and technical challenges in developing linkages between the growing collections of animal movement data and the large repositories of heterogeneous remote sensing observations, as well as in the developments of new statistical and computational methods for the analysis of movement in its environmental context. These challenges include retrieval, indexing, efficient storage, data integration, and analytical techniques., Results: This paper contributes to movement ecology research by presenting a new publicly available system, Environmental-Data Automated Track Annotation (Env-DATA), that automates annotation of movement trajectories with ambient atmospheric observations and underlying landscape information. Env-DATA provides a free and easy-to-use platform that eliminates technical difficulties of the annotation processes and relieves end users of a ton of tedious and time-consuming tasks associated with annotation, including data acquisition, data transformation and integration, resampling, and interpolation. The system is illustrated with a case study of Galapagos Albatross (Phoebastria irrorata) tracks and their relationship to wind, ocean productivity and chlorophyll concentration. Our case study illustrates why adult albatrosses make long-range trips to preferred, productive areas and how wind assistance facilitates their return flights while their outbound flights are hampered by head winds., Conclusions: The new Env-DATA system enhances Movebank, an open portal of animal tracking data, by automating access to environmental variables from global remote sensing, weather, and ecosystem products from open web resources. The system provides several interpolation methods from the native grid resolution and structure to a global regular grid linked with the movement tracks in space and time. The aim is to facilitate new understanding and predictive capabilities of spatiotemporal patterns of animal movement in response to dynamic and changing environments from local to global scales.

As more registered nurses (RNs) return to school to obtain a bachelor of science in nursing (BSN), innovative ways must be found to support them in this endeavor. Barriers for RNs who return to school include scheduling of coursework and fear of failure. One school of nursing with a traditional BSN program reviewed its RN-BSN track, with its low retention and graduation rates. With input from nursing leaders and nurses in the community, the school applied for and was awarded a 3-year Health Resources and Services Administration grant to redesign the RN-BSN program. A hybrid classroom-online curriculum is offered in a structured, sequential format so that the RNs are admitted once a year and must complete the courses as a group, in a cohort. Data collected from evaluations showed that program support, technology support, and social support from peers encouraged the RNs to "stay the course," and 100% completed the requirements to graduate., (Copyright 2011, SLACK Incorporated.)

Motor vehicle crashes killed almost 5,000 pedestrians in 2005 in the United States. Pedestrian risk may be higher in areas characterized by urban sprawl. From 2000 to 2004, pedestrian fatality rates declined in the United States, but the Atlanta metropolitan statistical area did not experience the same decline. Pedestrian fatality rates for males, Hispanics, and the 15-34 and 35-54 year age groups were higher in Atlanta than in the United States overall. Pedestrian safety interventions should be targeted to high-risk populations and localized pedestrian settings.

Objectives: To determine incidence of child-related dog bites and sensitivities of 3 county health department dog-bite surveillance systems., Design: Retrospective study., Study Population: Child-related dog-bite data obtained from surveillance systems of 3 counties in Georgia in the year 2000., Procedure: To characterize the sensitivity of health department dog-bite surveillance systems, 9 other potential sources of dog-bite records that matched records by victim name, age, gender, and incident date were evaluated. The number of reported bites and the most productive sources for identifying additional cases were determined. The Chandra Sekar-Deming capture-recapture method was used to estimate the number of unreported bites, and estimates of dog-bite incidence rates were made., Results: 40, 36, and 185 dog bites were reported in the 3 counties, respectively. Capture-recapture calculations estimated an additional 9, 5, and 128 dog bites in these counties, respectively. Local health departments recorded 45.5% to 82.5% of dog bites. Local hospital emergency departments, police departments, and a rabies-testing laboratory received additional reports. Among these data sources, local hospital emergency department records were the best source for identifying additional cases., Conclusions and Clinical Relevance: Dog bites are a preventable cause of childhood injuries, and surveillance is a critical tool for tracking childhood dog bites in the community. Counties should use combined data from local health departments, local hospital emergency departments, and police departments to implement or revise dog-bite prevention programs.

Background: Bicycle-related head injuries cause >150 deaths and 45 000 nonfatal injuries among children in the United States annually. Although bicycle helmets are highly effective against head injury, only 24% of US children regularly wear one. Georgia mandated bicycle helmet use for children, effective July 1993. During that summer, 1 rural Georgia community passed an ordinance instructing police officers to impound the bicycle of any unhelmeted child. We evaluated the effect of active police enforcement of this ordinance, combined with a helmet giveaway and education program., Methods: During April 1997, approximately 580 children in kindergarten through grade 7 received free helmets, fitting instructions, and safety education. Police then began impounding bicycles of unhelmeted children. We conducted an observational study, unobtrusively observing helmet use just before helmet distribution, several times during the next 5 months, and once 2 years later., Results: Before the program began, none of 97 observed riders wore a helmet. During the next 5 months, helmet use among 358 observed children averaged 45% (range: 30%-71%), a significant increase in all race and gender groups. In contrast, adult use did not change significantly. Police impounded 167 bicycles during the study, an average of 1 per day. Two years after program initiation, 21 of 39 child riders (54%) were observed wearing a helmet., Conclusions: Without enforcement, the state and local laws did not prompt helmet use in this community, yet active police enforcement, coupled with helmet giveaways and education, was effective and lasting.