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The appearance of senescent cells in age-related diseases has spurred the search for compounds that can target senescent cells in tissues, termed senolytics. However, a major caveat with current senolytic screens is the use of cell lines as targets where senescence is induced in vitro, which does not necessarily reflect the identity and function of pathogenic senescent cells in vivo. Here, we developed a new pipeline leveraging a fluorescent murine reporter that allows for isolation and quantification of p16Ink4a+ cells in diseased tissues. By high-throughput screening in vitro, precision-cut lung slice (PCLS) screening ex vivo, and phenotypic screening in vivo, we identified a HSP90 inhibitor, XL888, as a potent senolytic in tissue fibrosis. XL888 treatment eliminated pathogenic p16Ink4a+ fibroblasts in a murine model of lung fibrosis and reduced fibrotic burden. Finally, XL888 preferentially targeted p16INK4a-hi human lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF), and reduced p16INK4a+ fibroblasts from IPF PCLS ex vivo. This study provides proof of concept for a platform where p16INK4a+ cells are directly isolated from diseased tissues to identify compounds with in vivo and ex vivo efficacy in mice and humans, respectively, and provides a senolytic screening platform for other age-related diseases.

The main objective of this study is to understand the interlinkages between different irrigation technologies and management systems and environmental outcomes. We use a unique and comprehensive household and plot-level dataset covering ten districts of Ethiopia complemented with remotely sensed data and qualitative information collected from the study sites. The econometric results show that compared to open-access plots equipped with pump irrigation, other irrigated configurations, and especially private groundwater-based systems, have higher vegetation cover and show less susceptibility to the most common environmental concerns mentioned in the survey regions: water logging, soil salinity, and erosion externalities.

This study was undertaken to address an issue of student retention and learning in undergraduate computer science (CS) courses. To improve students' CS learning experience, the goal of this case study was to support five CS faculty's integration of active learning into their teaching, using the Understanding by Design framework. We explored the CS faculty's considerations and experiences with active learning integration. The data included video conferencing recordings, syllabi data analysis, teacher interviews, and a focus group. The results showed that CS faculty considered three aspects in their active learning integration: (a) course structure and delivery format, (b) instructional approaches, and (c) authentic learning experiences for students. The CS faculty's primary challenge was ways to assess individual students' knowledge gained in team-based activities. We found a gradual adaptation of active learning in CS faculty's teaching practices and recognized that their development and change in pedagogies need time and personalized support.

TRIM21 is a pivotal effector in the immune system, orchestrating antibody-mediated responses and modulating immune signaling. In this comprehensive study, we focus on the interaction of TRIM21 with Fc engineered antibodies and subsequent implications for viral neutralization. Through a series of analytical techniques, including biosensor assays, mass photometry, and electron microscopy, along with structure predictions, we unravel the intricate mechanisms governing the interplay between TRIM21 and antibodies. Our investigations reveal that the TRIM21 capacity to recognize, bind, and facilitate the proteasomal degradation of antibody-coated viruses is critically dependent on the affinity and avidity interplay of its interactions with antibody Fc regions. We suggest a novel binding mechanism, where TRIM21 binding to one Fc site results in the detachment of PRYSPRY from the coiled-coil domain, enhancing mobility due to its flexible linker, thereby facilitating the engagement of the second site, resulting in avidity due to bivalent engagement. These findings shed light on the dual role of TRIM21 in antiviral immunity, both in recognizing and directing viruses for intracellular degradation, and demonstrate its potential for therapeutic exploitation. The study advances our understanding of intracellular immune responses and opens new avenues for the development of antiviral strategies and innovation in tailored effector functions designed to leverage TRIM21s unique binding mode.

Compilations of earthquake moment tensors from global and regional catalogs find pervasive non-double-couple (NDC) components with a mean deviation from a double-couple (DC) source of around 20%. Their distributions vary only slightly with magnitude, faulting mechanism, or geologic environments. This consistency suggests thatfor most earthquakes, especially smaller ones whose rupture processes are expected to be simpler, the NDC components are largely artifacts of the moment tensor inversion procedure. This possibility is also supported by the fact that NDC components for individual earthquakes with Mw

ABSTRACTSoil erosion and subsequent land degradation undermine efforts to ensure food security and environmental sustainability in Ethiopia. The government of Ethiopia has implemented extensive soil and water conservation (SWC) programs in severely degraded and food-insecure areas of the country, in some cases integrated with subsequent or parallel irrigation development. However, the effectiveness of these interventions has not been extensively evaluated. This study, therefore, evaluates the performance and impacts of SWC practices in terms of improving vegetation greenness and reducing soil erosion in Feresmay watershed in Ethiopia. Long-term Landsat-based Normalised Difference Vegetation Index (NDVI), Revised Universal Soil Loss Equation (RUSLE), and Soil and Water Assessment Tool (SWAT) were used for change-detection analysis before and after the implementation of various SWC interventions. The results revealed the positive impacts of SWC interventions in improving the vegetation greenness and soil erosion reduction although the outcome varied by intervention. Increased vegetation greenness was observed largely in areas where area closure with catchment treatment (ACCT) and impacts of irrigation (IRR) interventions are dominant, while relatively little impact was observed at the watershed level analysis. Although these interventions helped to reduce soil loss, the results highlighted the need for more SWC interventions to minimise further soil loss.

Abstract Ocean waves excite continuous globally observable seismic signals. We use data from 52 globally distributed seismographs to analyze the vertical component primary microseism wavefield at 14–20 s period between the late 1980s and August 2022. This signal is principally composed of Rayleigh waves generated by ocean wave seafloor tractions at less than several hundred meters depth, and is thus a proxy for near-coastal swell activity. Here we show that increasing seismic amplitudes at 3σ significance occur at 41 (79%) and negative trends occur at 3σ significance at eight (15%) sites. The greatest absolute increase occurs for the Antarctic Peninsula with respective acceleration amplitude and energy trends ( ± 3σ) of 0.037 ± 0.008 nm s−2y−1 (0.36 ± 0.08% y−1) and 4.16 ± 1.07 nm2 s−2y−1 (0.58 ± 0.15% y−1), where percentage trends are relative to historical medians. The inferred global mean near-coastal ocean wave energy increase rate is 0.27 ± 0.03% y−1 for all data and is 0.35 ± 0.04% y−1 since 1 January 2000. Strongly correlated seismic amplitude station histories occur to beyond 50∘ of separation and show regional-to-global associations with El Niño and La Niña events.

The Doctor of Education (EdD) in Educational Leadership at East Carolina University incorporated advising into the admissions process through the first two semesters of the program. This study examined how, through the first year of implementation of this process, student knowledge of the role of the scholarly practitioner evolved from pre-admission advising through the second semester of this CPED-influenced EdD program. CPED is the Carnegie Project for the Educational Doctorate, a consortium of colleges of education which aims to prepare scholarly practitioners to solve problems of practice through the lens of equity, ethics, and social justice (CPED, 2009; Hoffman & Perry, 2016). The study describes how faculty utilized the Model of Improvement framework with three Plan-Do-Study-Act cycles to intentionally teach this concept. The results of this study indicated that there was a mindset change for students from practitioners to scholarly practitioners. Accordingly, the findings herein may be beneficial to educational leadership doctoral programs in replicating the program's successes with growing practitioners into scholarly practitioners through embedded activities from admission through early coursework.

Groundwater management is highly complex, with many users sharing the same resource often with limited understanding of their interconnectedness. Behavioral experiments (games) that simulate real-life common-pool resource use have shown promise as an experiential learning tool for improving resource governance. This study pilots an experiential learning intervention in Ethiopia using a groundwater game to help raise awareness of groundwater over-extraction and improve understanding of the importance of collective action in governance. In the Meki River catchment in Ethiopia, small-scale irrigation is expanding, but overextraction and competition over groundwater have not yet reached alarming levels. The groundwater game, adapted from India and including the addition of a rule-making round, was played in 15 villages with 30 groups. The game was accompanied by subsequent community-wide debriefing in each village to reflect on the experience and lessons learned, which stimulated discussions about groundwater governance. We surveyed participants to capture individual mental models regarding groundwater use and management, as well as any immediate learning effects. Focus group discussions in each village prior to the intervention and again six months after the intervention assessed possible lasting effects. The findings indicate cognitive, normative and relational learning, including increased understanding of groundwater dynamics (such as the joint effect of diverse water uses and users), the importance of collective action in resource management, and the benefits of communication. We find gendered differences in decision-making about resource extraction in the game and development of group-level resource management, confirming the need for gender-responsive approach to sustainable groundwater management interventions. We discuss community-wide learning and institution-building, and considerations for future intervention designs. We recommend embedding experiential learning, facilitated by local extension officers and other practitioners, in intervention packages that include both technical assistance on water-conserving technologies and groundwater management approaches and support in building communities’ institutional capacity.

Irrigation expansion is critical for agricultural and rural development, food and nutrition security, and climate change adaptation in Sub-Saharan Africa (SSA). Lack of accessible energy for irrigation development due to limited off- and on-grid infrastructure and the resulting dependence on costly fuel-based irrigation have been key inhibiting factors for irrigation expansion in the region. Off-grid solar-powered irrigation pumps (SIPs) can overcome many of the energy access and other challenges in the region, but their uptake has been slow. Given the nascent development of the solar irrigation sector in SSA, this paper combines a review of the peer-reviewed and grey literature with key informant interviews to identify systemic barriers to the adoption and growth of solar-powered irrigation. We identify uncovered risks, lack of incentives, and lack of capacity as the key factors limiting the adoption of solar-powered irrigation. Moreover, despite significant global cost reductions, solar-powered irrigation systems remain costly in SSA due to limited market development and geographical constraints. Lack of regulation and low investment in building local institutions and value chains further affect uptake and inhibit leveraging the energy transition for ensuring food security and agriculture-led poverty alleviation in SSA. We propose a move away from thinking of SIPs as “silver bullets” and towards a systems approach and the design of context-specific solutions to address risks, incentives and capacity challenges.

Abstract Animal personality traits are sometimes linked to an individual’s degree of plasticity, with certain personality types being more plastic than others. In territorial species, consistently high levels of aggression might increase the risk of harmful fights, while consistently low aggression might lead to the loss of a territory. Consequently, reacting plastically with an appropriate territorial response should be beneficial to avoid these risks. An integrative investigation of both personality traits and plasticity can help us better understand the dynamics of aggressive interactions during male-male competition. Here, we used a free-ranging Neotropical poison frog population to investigate the role of plasticity in male territorial aggression towards intruders. We conducted repeated standardized territorial intrusion experiments mimicking frogs of different body sizes via playback calls with different peak frequencies. We found individual repeatability for the latency to reach and approach a simulated intruder and observed that both aggressive and less aggressive males decreased their level of aggression towards big intruders. However, our results do not support a correlation between personality and plasticity in the context of male territory defense during the breeding season. We discuss how such a correlation between personality and plasticity might be conditional on the costs and benefits across contexts.

Abstract One of the most extreme adaptations to terrestriality in anurans is direct development, where eggs from terrestrial clutches entirely circumvent an aquatic tadpole stage and directly develop into small froglets. We here report the first case of egg‐burying behaviour in a neotropical direct‐developing frog with subsequent short‐term maternal care. An amplectant pair of Pristimantis chocoensis was found at the Reserva Canandé in Esmeraldas, Ecuador, and we recorded oviposition and the later rotation and active burying of the clutch by the female. Both parents remained close to the nest area the following day. This rare observation sheds light on the complex but often cryptic reproductive behaviours of terrestrial amphibians and suggests that the evolution of direct development has selected for highly specialized forms of parental care.

AbstractThis study was undertaken to address an issue of student retention and learning in undergraduate computer science (CS) courses. To improve students’ CS learning experience, the goal of this case study was to support five CS faculty’s integration of active learning into their teaching, using the Understanding by Design framework. We explored the CS faculty’s considerations and experiences with active learning integration. The data included video conferencing recordings, syllabi data analysis, teacher interviews, and a focus group. The results showed that CS faculty considered three aspects in their active learning integration: (a) course structure and delivery format, (b) instructional approaches, and (c) authentic learning experiences for students. The CS faculty’s primary challenge was ways to assess individual students’ knowledge gained in team-based activities. We found a gradual adaptation of active learning in CS faculty’s teaching practices and recognized that their development and change in pedagogies need time and personalized support.

Territorial behaviour has been widely described across many animal taxa, where the acquisition and defence of territory are critical for the fitness of an individual. Extensive evidence suggests that androgens are involved in the modulation of territorial behaviour in male vertebrates. A short-term increase of androgen following a territorial encounter appears to favour the outcome of a challenge. The “Challenge Hypothesis” outlines the relationship between androgen and social challenges in male vertebrates. Here we tested the challenge hypothesis in the highly territorial poison frog, Allobates femoralis, in its natural habitat by exposing males to simulated territorial intrusions in the form of acoustic playbacks. We quantified repeatedly androgen concentrations of individual males via a non-invasive water-borne sampling approach. Our results show that A. femoralis males exhibited a positive behavioural and androgenic response after being confronted with simulated territorial intrusions, providing support for the Challenge Hypothesis in a territorial frog.

The Grand Ethiopian Renaissance Dam (GERD) on the Nile is expected to influence many ecosystem services, such as flood regulation, hydro-electricity production, food supply, and habitat provision, among others. Understanding these impacts (positive and negative) requires a comprehensive evaluation framework. This study develops and applies an integrated simulation framework for assessing the impacts of the GERD on Sudan, focusing on the simultaneous economywide effects of riverine flood hazards, irrigation water supply, hydropower generation, and floodplain-dependent industries, namely traditional fired clay brick production. The simulation framework incorporates three models: a river infrastructure system model, a flood model, and a Computable General Equilibrium Model. Results indicate positive impacts for hydropower generation and flood control, marginal benefits for water supply to existing irrigation, and negative consequences for brick production and the construction sector. Assuming that the GERD starts its long-term operation in 2025, we find an overall positive economic impact on Sudan’s Gross Domestic Product in 2025, with an increase of up to just over 0.1%, subject to river flow conditions. Recognizing the differences in impacts across sectors and income groups, the study emphasizes the need for interventions that ameliorate negative effects. While the study captures several impacts, other effects on the environment, recession agriculture, and soil fertility require further investigation. Still, our findings underscore the importance of adopting an integrated simulation approach to dam evaluation, acknowledging the interconnected nature of water and related sectors in national economies.

Socio-economic changes, technical progress, and a variety of funding and planning interventions have significantly changed land use in Central Europe since World War II. The aim of this study was to illustrate these changes in the Alpine foothills in Bavaria and to calculate the effects of these changes on soil erosion. This was performed in a two-step procedure: a GIS-based orthophoto evaluation and a cause–effect model using the revised universal soil loss equation (RUSLE). Key findings were that field sizes (+370%) and lengths (+35%) have changed significantly since the 1960s. Moreover, the uninterrupted runoff paths on arable land have increased in length by about 70% on average, with corresponding effects on soil erosion. The discussion shows that the possibilities for erosion control measures in the field are already severely limited due to the effects of the climate crisis and structural changes in agriculture. Furthermore, the often-assumed rule, according to which only a small part of the arable land causes a large share of the eroded material, was largely confirmed. The findings underline the overlapping impacts of land use change and climate crisis on agriculture erosions rates with the need for integrative and adaptive management.

Faunas of oceanic islands have a high proportion of endemic species which contribute to the uniqueness of island communities. Island species are particularly naïve and vulnerable to alien predators, such as cats (Felis catus). On large, inhabited islands, where the complete eradication of feral cat populations is not considered feasible, control represents the best management option to lower their detrimental effects on native fauna. The first objective of our study was to investigate population genetics of feral cats of Réunion Island. The second objective was to understand the space use of feral cats established near the breeding colonies of the two endemic and endangered seabirds of Réunion Island, the Barau’s Petrel (Pterodroma baraui) and the Mascarene Petrel (Pseudobulweria aterrima). We evaluated genetic diversity, population structure and gene flow amongst six groups of feral cats located at a maximum of 10 km from known petrel colonies. We also analysed the behaviour and space use of one of these feral cat groups using camera-trap data and Spatially Explicit Capture-Recapture (SECR) models. Genetic analyses revealed that feral cats were structured in three genetic clusters explained mostly by the island topography. Two clusters were observed at five sampled sites, suggesting high connectivity amongst these sites. The last cluster was found in only one site, suggesting high isolation. This site was a remote mountain area located in the vicinity of one of the main Barau’s Petrel colonies. The behavioural study was conducted on this isolated feral cat population. Mark recapture analysis suggested that feral cats were present at low density and had large home ranges, which is probably explained by reduced food availability. Finally, we make several recommendations for refining feral cat management programmes on inhabited islands.

Selecting economic policies to achieve sustainable development is challenging due to the many sectors involved and the trade-offs implied. Artificial intelligence combined with economy-wide computer simulations can help.

The purpose of the study was to determine whether the study of diversity topics embedded in a Principal Preparation Program (PPP) internship changed candidates' self-awareness of their biases in educational environments and the biases they observed in their school community. In this study PPP candidates' perceptions of their biases and those of their schools were assessed at the beginning and end of the internship. The Anti-Defamation League's (ADL), Assessing Yourself and Your School Checklist, were utilized to obtain candidates self-perceptions. Throughout the internship monthly learning activities, PPP candidates studied various diversity topics that impact schools. Descriptive statistics were utilized to complete a pretest-posttest comparison to determine any changes toward their biases. The findings of this study demonstrated that diversity topics embedded in an PPP internship increased candidates' self-awareness of their personal biases in educational environments and the biases they observe in their school community. The study of diversity topics broadened PPP candidates' awareness of the challenges faced by groups and individuals in their school communities.

Objective: Unilateral strength training has been shown to be more effective than bilateral training to increase strength in healthy people. The aims of this study were to test the feasibility of unilateral strength training during total knee arthroplasty (TKA) rehabilitation and compare it with standard bilateral training. Methods: Twenty-four TKA patients from an inpatient rehabilitation programme were randomly assigned to unilateral and bilateral strength training groups. Both groups completed 6 strength training sessions during 3 weeks of rehabilitation. Isometric strength, knee joint flexibility, knee circumference, chair rise and walking abilities, and perceived exertion and pain were assessed before and after the training period. Results: Both training groups increased isometric strength of both legs (+17–25%) and flexibility of the affected leg (+7.6%). Improvements in isometric strength of the healthy leg (+23% vs +11%) and flexibility of the affected leg (+10.7% vs +4.5%) were greater in the unilateral training group. Chair rise and 2-min walk test results improved in both groups, to the same extent. Perceived exertion decreased only in the unilateral training group (–20%), while perceived pain did not change in either group. Conclusion: This study showed the feasibility of unilateral strength training in TKA rehabilitation. Strength and flexibility improved similarly or better with unilateral strength training compared with standard bilateral strength training. Future studies should analyse the efficacy of prolonged unilateral strength training following TKA. LAY ABSTRACT The rehabilitation process following a total knee replacement surgery is aimed at regaining strength and flexibility of the knee joint and improving the movements of daily living, such as walking and standing up from a chair. However, to date, it is not known which kind of strength training is most effective in achieving this aim within a rehabilitation programme. During standard rehabilitation, both legs are trained. The current study tested whether training of the affected leg only is feasible, and compared it with standard strength training of both legs. Training the affected leg only resulted in greater improvements in flexibility and similar or greater improvements in strength. Both types of training resulted in improvements in walking and standing up from a chair. In conclusion, strength training of the affected leg only is a feasible alternative to standard strength training with both legs in total knee replacement rehabilitation.

Sex differences in vertebrate spatial abilities are typically interpreted under the adaptive specialization hypothesis, which posits that male reproductive success is linked to larger home ranges and better navigational skills. The androgen spillover hypothesis counters that enhanced male spatial performance may be a byproduct of higher androgen levels. Animal groups that include species where females are expected to outperform males based on life-history traits are key for disentangling these hypotheses. We investigated the association between sex differences in reproductive strategies, spatial behavior, and androgen levels in three species of poison frogs. We tracked individuals in natural environments to show that contrasting parental sex roles shape sex differences in space use, where the sex performing parental duties shows wider-ranging movements. We then translocated frogs from their home areas to test their navigational performance and found that the caring sex outperformed the non-caring sex only in one out of three species. In addition, males across species displayed more explorative behavior than females and androgen levels correlated with explorative behavior and homing accuracy. Overall, we reveal that poison frog reproductive strategies shape movement patterns but not necessarily navigational performance. Together this work suggests that prevailing adaptive hypotheses provide an incomplete explanation of sex differences in spatial abilities.

This paper reports on a study completed with principal preparation students to measure the change in their beliefs about how to provide leadership that affirms diverse students and families in schools. The principal preparation program (PPP) in this study redesigned the internship to include crucial conversations around diversity and social justice. Students were prompted to reflect on social justice issues using a lens of school safety and bullying [Payne, E. C., and M. J. Smith. 2018. "Refusing Relevance: School Administrator Resistance to Offering Professional Development Addressing LGBTQ Issues in Schools." "Educational Administration Quarterly" 54 (2): 183-215]. The goal for the PPP was to develop leadership skills towards creating inclusive and integrated schools that grapple with diversity issues with the best interest of all stakeholders. The purpose of this study was to determine whether the study of diversity topics embedded in a PPP internship altered candidates' self-awareness of their biases in educational settings, utilising the inside-out approach [Lindsey, R. B., K. Nuri-Robins, and R. D. Terrell. 2009. "Cultural Proficiency: A Manual for School Leaders." Thousand Oaks: Corwin Press].

This work documents the first version of the U.S. Department of Energy (DOE) new Energy Exascale Earth System Model (E3SMv1). We focus on the standard resolution of the fully coupled physical model designed to address DOE mission-relevant water cycle questions. Its components include atmosphere and land (110-km grid spacing), ocean and sea ice (60 km in the midlatitudes and 30 km at the equator and poles), and river transport (55 km) models. This base configuration will also serve as a foundation for additional configurations exploring higher horizontal resolution as well as augmented capabilities in the form of biogeochemistry and cryosphere configurations. The performance of E3SMv1 is evaluated by means of a standard set of Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima simulations consisting of a long preindustrial control, historical simulations (ensembles of fully coupled and prescribed SSTs) as well as idealized CO2 forcing simulations. The model performs well overall with biases typical of other CMIP-class models, although the simulated Atlantic Meridional Overturning Circulation is weaker than many CMIP-class models. While the E3SMv1 historical ensemble captures the bulk of the observed warming between preindustrial (1850) and present day, the trajectory of the warming diverges from observations in the second half of the twentieth century with a period of delayed warming followed by an excessive warming trend. Using a two-layer energy balance model, we attribute this divergence to the model's strong aerosol-related effective radiative forcing (ERFari+aci = −1.65 W/m2) and high equilibrium climate sensitivity (ECS = 5.3 K).

We present MPAS-Seaice, a sea-ice model which uses the Model for Prediction Across Scales (MPAS) framework and spherical centroidal Voronoi tessellation (SCVT) unstructured meshes. As well as SCVT meshes, MPAS-Seaice can run on the traditional quadrilateral grids used by sea-ice models such as CICE. The MPAS-Seaice velocity solver uses the elastic–viscous–plastic (EVP) rheology and the variational discretization of the internal stress divergence operator used by CICE, but adapted for the polygonal cells of MPAS meshes, or alternatively an integral (“finite-volume”) formulation of the stress divergence operator. An incremental remapping advection scheme is used for mass and tracer transport. We validate these formulations with idealized test cases, both planar and on the sphere. The variational scheme displays lower errors than the finite-volume formulation for the strain rate operator but higher errors for the stress divergence operator. The variational stress divergence operator displays increased errors around the pentagonal cells of a quasi-uniform mesh, which is ameliorated with an alternate formulation for the operator. MPAS-Seaice shares the sophisticated column physics and biogeochemistry of CICE and when used with quadrilateral meshes can reproduce the results of CICE. We have used global simulations with realistic forcing to validate MPAS-Seaice against similar simulations with CICE and against observations. We find very similar results compared to CICE, with differences explained by minor differences in implementation such as with interpolation between the primary and dual meshes at coastlines. We have assessed the computational performance of the model, which, because it is unstructured, runs with 70 % of the throughput of CICE for a comparison quadrilateral simulation. The SCVT meshes used by MPAS-Seaice allow removal of equatorial model cells and flexibility in domain decomposition, improving model performance. MPAS-Seaice is the current sea-ice component of the Energy Exascale Earth System Model (E3SM).