Getting in the zone: flow experiences of high school students in language arts

There are severe gaps in reading achievement among students based on ability, race, and income levels. As a result, many high school students with reading difficulties, particularly those who are minorities and living in poverty, are not able to read with the same level of skill as their peers, which can affect their chances of success later in life. Flow theory may offer guidance regarding how to engage and motivate these students in school, particularly when it comes to reading. When individuals have a flow experience, Csikszentmihalyi suggests that intrinsic motivation to participate in that activity will increase and more participation may translate to improved performance. In this mixed methods case study, participants included a language arts teacher and 22 10th-grade students attending language arts classes at a Title I public charter school. A reading assessment was administered along with surveys measuring self-efficacy, motivation, and flow. On three occasions, students’ flow scores were evaluated and compared. Data were analyzed using descriptive and inferential statistics, including hierarchical linear modeling and mediation analysis. Follow-up interviews were conducted with 13 participants to better understand their flow experiences including what motivates and engages them across contexts. These data were analyzed via domain analysis. Results indicated that although there were no differences in flow across activities, there were differences based on individual characteristics, including intrinsic motivation to read and perceptions of skill/challenge balance. In addition, reading ability and flow together explained a substantial portion of variability in reading motivation overall. Interview data centered on students being driven to succeed. Other themes identified related to teacher attributes, motivation, engagement, reading, and flow. Implications and suggestions for practice are also discussed

A scientific synthesis of marine protected areas in the United States: status and recommendations

Marine protected areas (MPAs) are a key tool for achieving goals for biodiversity conservation and human well-being, including improving climate resilience and equitable access to nature. At a national level, they are central components in the U.S. commitment to conserve at least 30% of U.S. waters by 2030. By definition, the primary goal of an MPA is the long-term conservation of nature; however, not all MPAs provide the same ecological and social benefits. A U.S. system of MPAs that is equitable, well-managed, representative and connected, and includes areas at a level of protection that can deliver desired outcomes is best positioned to support national goals. We used a new MPA framework, The MPA Guide, to assess the level of protection and stage of establishment of the 50 largest U.S. MPAs, which make up 99.7% of the total U.S. MPA area (3.19 million km2). Over 96% of this area, including 99% of that which is fully or highly protected against extractive or destructive human activities, is in the central Pacific ocean. Total MPA area in other regions is sparse – only 1.9% of the U.S. ocean excluding the central Pacific is protected in any kind of MPA (120,976 km2). Over three quarters of the non-central Pacific MPA area is lightly or minimally protected against extractive or destructive human activities. These results highlight an urgent need to improve the quality, quantity, and representativeness of MPA protection in U.S. waters to bring benefits to human and marine communities. We identify and review the state of the science, including focal areas for achieving desired MPA outcomes and lessons learned from places where sound ecological and social design principles come together in MPAs that are set up to achieve national goals for equity, climate resilience, and biodiversity conservation. We recommend key opportunities for action specific to the U.S. context, including increasing funding, research, equity, and protection level for new and existing U.S. MPAs

FOXC2 promotes vasculogenic mimicry and resistance to anti-angiogenic therapy.

Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood vessels, and their presence is generally associated with poor patient prognosis. Here we show that the transcription factor, Foxc2, promotes VM in diverse solid tumor types by driving ectopic expression of endothelial genes in tumor cells, a process that is stimulated by hypoxia. VM-proficient tumors are resistant to anti-angiogenic therapy, and suppression of Foxc2 augments response. This work establishes co-option of an embryonic endothelial transcription factor by tumor cells as a key mechanism driving VM proclivity and motivates the search for VM-inhibitory agents that could form the basis of combination therapies with anti-angiogenics

ActRIIB:ALK4-Fc alleviates muscle dysfunction and comorbidities in murine models of neuromuscular disorders

Patients with neuromuscular disorders suffer from a lack of treatment options for skeletal muscle weakness and disease comorbidities. Here, we introduce as a potential therapeutic agent a heterodimeric ligand-trapping fusion protein, ActRIIB:ALK4-Fc, which comprises extracellular domains of activin-like kinase 4 (ALK4) and activin receptor type IIB (ActRIIB), a naturally occurring pair of type I and II receptors belonging to the TGF-β superfamily. By surface plasmon resonance (SPR), ActRIIB:ALK4-Fc exhibited a ligand binding profile distinctly different from that of its homodimeric variant ActRIIB-Fc, sequestering ActRIIB ligands known to inhibit muscle growth but not trapping the vascular regulatory ligand bone morphogenetic protein 9 (BMP9). ActRIIB:ALK4-Fc and ActRIIB-Fc administered to mice exerted differential effects - concordant with SPR results - on vessel outgrowth in a retinal explant assay. ActRIIB:ALK4-Fc induced a systemic increase in muscle mass and function in wild-type mice and in murine models of Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis (ALS), and disuse atrophy. Importantly, ActRIIB:ALK4-Fc improved neuromuscular junction abnormalities in murine models of DMD and presymptomatic ALS and alleviated acute muscle fibrosis in a DMD model. Furthermore, in combination therapy ActRIIB:ALK4-Fc increased the efficacy of antisense oligonucleotide M12-PMO on dystrophin expression and skeletal muscle endurance in an aged DMD model. ActRIIB:ALK4-Fc shows promise as a therapeutic agent, alone or in combination with dystrophin rescue therapy, to alleviate muscle weakness and comorbidities of neuromuscular disorders

Human and biophysical legacies shape contemporary urban forests: a literature synthesis

Understanding how urban forests developed their current patterns of tree canopy cover, species composition,and diversity requires an appreciation of historical legacy effects. However, analyses of current urban forestcharacteristics are often limited to contemporary socioeconomic factors, overlooking the role of history. Theinstitutions, human communities, and biophysical conditions of cities change over time, creating layers of legacieson the landscape, shifting urban forests through complex interactive processes and feedbacks. Urbangreen spaces and planted trees can persist long after their establishment, meaning that today’s mature canopyreflects conditions and decisions from many years prior. In this synthesis article, we discuss some of the majorhistorical human and biophysical drivers and associated legacy effects expressed in present urban forest patterns,highlighting examples in the United States and Canada. The bioregional context – native biome, climate, topography,initial vegetation, and pre-urbanization land use – represents the initial conditions in which a cityestablished and grew, and this context influences how legacy effects unfold. Human drivers of legacy effects canreflect specific historical periods: colonial histories related to the symbolism of certain species, and the urbanparks and civic beautification movements. Other human drivers include phenomena that cut across time periodssuch as neighborhood urban form and socioeconomic change. Biophysical legacy effects include the consequencesof past disturbances such as extreme weather events and pest and disease outbreaks. Urban treeprofessionals play a major role in many legacy effects by mediating the interactions and feedbacks betweenbiophysical and human drivers. We emphasize the importance of historical perspectives to understand past drivers that have produced current urban forest patterns, and call for interdisciplinary and mixed methodsresearch to unpack the mechanisms of long-term urban forest change at intra- and inter-city scales

Lineage Plasticity in SCLC Generates Non-Neuroendocrine Cells Primed for Vasculogenic Mimicry

INTRODUCTION: Vasculogenic mimicry (VM), the process of tumor cell transdifferentiation to endow endothelial-like characteristics supporting de novo vessel formation, is associated with poor prognosis in several tumor types, including SCLC. In genetically engineered mouse models (GEMMs) of SCLC, NOTCH, and MYC co-operate to drive a neuroendocrine (NE) to non-NE phenotypic switch, and co-operation between NE and non-NE cells is required for metastasis. Here, we define the phenotype of VM-competent cells and molecular mechanisms underpinning SCLC VM using circulating tumor cell-derived explant (CDX) models and GEMMs.METHODS: We analyzed perfusion within VM vessels and their association with NE and non-NE phenotypes using multiplex immunohistochemistry in CDX, GEMMs, and patient biopsies. We evaluated their three-dimensional structure and defined collagen-integrin interactions.RESULTS: We found that VM vessels are present in 23/25 CDX models, 2 GEMMs, and in 20 patient biopsies of SCLC. Perfused VM vessels support tumor growth and only NOTCH-active non-NE cells are VM-competent in vivo and ex vivo, expressing pseudohypoxia, blood vessel development, and extracellular matrix organization signatures. On Matrigel, VM-primed non-NE cells remodel extracellular matrix into hollow tubules in an integrin β1-dependent process.CONCLUSIONS: We identified VM as an exemplar of functional heterogeneity and plasticity in SCLC and these findings take considerable steps toward understanding the molecular events that enable VM. These results support therapeutic co-targeting of both NE and non-NE cells to curtail SCLC progression and to improve the outcomes of patients with SCLC in the future.</p