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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 body-wave magnitude (mb) is a long-standing network-averaged, amplitude-based magnitude used to estimate the magnitude of seismic sources from teleseismic observations. The U.S. Geological Survey National Earthquake Information Center (NEIC) relies on mb in its global real-time earthquake monitoring mission. Although waveform modeling-based moment magnitudes are the modern standard to characterize earthquake size, mb is important because (1) in many cases, waveform modeling is not possible (e.g., low signal-to-noise events), (2) mb is applicable over a broad range of magnitudes, ∼M 4–7, and (3) there is a many decades-long history of estimating mb magnitudes. We use the NEIC Preliminary Determination of Epicenters earthquake catalog to investigate the uncertainty in NEIC station mb measurements. We show that mb measurements are spatially correlated, which can bias event mb, and we describe an empirical relation between this spatial correlation and station-to-station distance. We further describe an approach to mitigate bias from the spatial correlation. Accounting for the spatial covariance of observations can change the event mb from −0.15 to 0.07 mb units (10th to 90th percentile) for smaller events (mb≤4.5). These smaller events have the largest mb standard deviations ranging from 0.05 to 0.15 mb units (10th to 90th percentile).

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.

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.

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.

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.

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.

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

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.

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.

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 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.