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Building artificial neurons and synapses is key to achieving the promise of energy efficiency and acceleration envisioned for brain-inspired information processing. Emulating the spiking behavior of biological neurons in physical materials requires precise programming of conductance nonlinearities. Strong correlated solid-state compounds exhibit pronounced nonlinearities such as metal-insulator transitions arising from dynamic electron-electron and electron-lattice interactions. However, a detailed understanding of atomic rearrangements and their implications for electronic structure remains obscure. In this work, we unveil discontinuous conductance switching from an antiferromagnetic insulator to a paramagnetic metal in ε-Cu0.9V2O5. Distinctively, fashioning nonlinear dynamical oscillators from entire millimeter-sized crystals allows us to map the structural transformations underpinning conductance switching at an atomistic scale using single-crystal X-ray diffraction. We observe superlattice ordering of Cu ions between [V4O10] layers at low temperatures, a direct result of interchain Cu-ion migration and intrachain reorganization. The resulting charge and spin ordering along the vanadium oxide framework stabilizes an insulating state. Using X-ray absorption and emission spectroscopies, assigned with the aid of electronic structure calculations and measurements of partially and completely decuprated samples, we find that Cu 3d and V 3d orbitals are closely overlapped near the Fermi level. The filling and overlap of these states, specifically the narrowing/broadening of V 3dxy states near the Fermi level, mediate conductance switching upon Cu-ion rearrangement. Understanding the mechanisms of conductance nonlinearities in terms of ion motion along specific trajectories can enable the atomistic design of neuromorphic active elements through strategies such as cointercalation and site-selective modification.

Teaching and learning online is an increasingly important aspect of higher education, especially post-COVID-19. Previous studies have demonstrated the importance of Technological Pedagogical Content Knowledge (TPACK) for effective online teaching. However, the contextual factors impacting TPACK have not been adequately explored. The purpose of this quantitative study was to determine if the contextual factor of institutional culture impacts TPACK among online higher education faculty at institutions in the southeastern United States as well as to what extent specific dimensions of institutional culture affect TPACK levels. Data were collected using an anonymous online survey that was shared with potential participants through email and social media. Data were analyzed using a multiple linear regression model to determine significance between the independent variables, the seven dimensions of institutional culture, and the dependent variable, TPACK. Results indicated that significance was found between two individual elements of institutional culture and TPACK: (1) collaboration and team learning and (2) connection between the organization and its environment. These findings indicate that higher education administrators should focus efforts on creating opportunities for faculty to engage in professional development and move beyond siloed work to collaborative projects. Administrators should also ensure that the institution is connected to the local, regional, and global community through aligned institutional goals with the needs of the community and establishing opportunities for faculty to connect globally. Future research should focus on exploring the relationship between specific aspects of institutional culture that may impact quality online teaching.

In spliceosome assembly, the 5 splice site is initially recognized by U1 snRNA. U1 leaves the spliceosome during the assembly process, therefore other factors contribute to the maintenance of 5 splice site identity as it is loaded into the catalytic site. Recent structural data suggest that human tri-snRNP 27K (SNRP27) M141 and SNU66 H734 interact to stabilize the U4/U6 quasi-pseudo knot at the base of the U6 snRNA ACAGAGA box in pre-B complex. Previously, we found that mutations in Caenorhabditis elegans at SNRP-27 M141 promote changes in alternative 5ss usage. We tested whether the potential interaction between SNRP-27 M141 and SNU-66 H765 (the C. elegans equivalent position to human SNU66 H734) contributes to maintaining 5 splice site identity during spliceosome assembly. We find that SNU-66 H765 mutants promote alternative 5 splice site usage. Many of the alternative 5 splicing events affected by SNU-66(H765G) overlap with those affected SNRP-27(M141T). Double mutants of snrp-27(M141T) and snu-66(H765G) are homozygous lethal. We hypothesize that mutations at either SNRP-27 M141 or SNU-66 H765 allow the spliceosome to load alternative 5 splice sites into the active site. Tests with mutant U1 snRNA and swapped 5 splice sites indicate that the ability of SNRP-27 M141 and SNU-66 H765 mutants to affect a particular 5 splice alternative splicing event is dependent on both the presence of a weaker consensus 5ss nearby and potentially nearby splicing factor binding sites. Our findings confirm a new role for the C terminus of SNU-66 in maintenance of 5 splice site identity during spliceosome assembly.

Type 1 diabetes (T1D) is a prototypic T cell-mediated autoimmune disease. Because the islets of Langerhans are insulated from blood vessels by a double basement membrane and lack detectable lymphatic drainage, interactions between endocrine and circulating T cells are not permitted. Thus, we hypothesized that initiation and progression of anti-islet immunity required islet neolymphangiogenesis to allow T cell access to the islet. Combining microscopy and single cell approaches, the timing of this phenomenon in mice was situated between 5 and 8 wk of age when activated anti-insulin CD4 T cells became detectable in peripheral blood while peri-islet pathology developed. This peri-insulitis, dominated by CD4 T cells, respected the islet basement membrane and was limited on the outside by lymphatic endothelial cells that gave it the attributes of a tertiary lymphoid structure. As in most tissues, lymphangiogenesis seemed to be secondary to local segmental endothelial inflammation at the collecting postcapillary venule. In addition to classic markers of inflammation such as CD29, V-CAM, and NOS, MHC class II molecules were expressed by nonhematopoietic cells in the same location both in mouse and human islets. This CD45- MHC class II+ cell population was capable of spontaneously presenting islet Ags to CD4 T cells. Altogether, these observations favor an alternative model for the initiation of T1D, outside of the islet, in which a vascular-associated cell appears to be an important MHC class II-expressing and -presenting cell.

Abstract Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals. By comparing MN methylation with an atlas of tissue methylation we have derived a MN-specific signature of hypomethylated genomic regions, which accords with genes important for MN function. Through simulation we have optimised the selection of regions for biomarker detection in plasma and CSF cell-free DNA (cfDNA). However, we show that MN-derived DNA is not detectable via WGBS in plasma cfDNA. In support of our experimental finding, we show theoretically that the relative sparsity of lower MN sets a limit on the proportion of plasma cfDNA derived from MN which is below the threshold for detection via WGBS. Our findings are important for the ongoing development of ALS biomarkers. The MN-specific hypomethylated genomic regions we have derived could be usefully combined with more sensitive detection methods and perhaps with study of CSF instead of plasma. Indeed we demonstrate that neuronal-derived DNA is detectable in CSF. Our work is relevant for all diseases featuring death of rare cell-types.

Social media has undoubtedly shifted the landscape of educator professional development in the 21st century. The establishment and development of identifiable professional learning communities (PLCs) like the #SSChat social studies community on Twitter enables educators to connect and collaborate with other professionals across the globe from their own mobile device. The purpose of this study was to determine the demographic features of the #SSChat members. Moreover, we sought to determine if there were any significant differences in #SSChat member's perceived 'Sense of Community' (SOC) based on those demographics. No statistically significant findings were discovered. Still, the demographic data provide good discussions.

Technology integration has received a significant amount of money from the budgets of schools in the United States, even prior to COVID-19. Social media as an instructional tool was also receiving growing attention. However, since COVID-19 it seems that there is an even larger shift in the calls to use social media. The purpose of this survey study was to report K-12 Tennessee social studies teachers' self-reported social media use just prior to the COVID-19. Moreover, we compared teachers' use of social media based on geography, grade level and teaching experience. Findings suggest that teachers rarely used social media in their teaching; however, statistically significant findings were discovered based on teaching experience.

In July 2022, the University of Tennessee and the Tennessee Geographic Alliance hosted a three-week summer institute funded by the National Endowment for Humanities (NEH) as part of its "A More Perfect Union" initiative to promote a deeper understanding of United States history and culture. Eighteen K-12 educators from across the country came to Knoxville to explore "The Role of Geographic Mobility in the African American Freedom Struggle." The institute focused on Movement as one of geography's five fundamental themes and highlighted the central role that migration, transportation, and travel and tourism have played in maintaining structural racism and facilitating Black antiracist resistance, self-determination, and world- making across multiple scales and historical periods. This article examines the NEH Institute.

There is a renewed interest for the use of inquiry in social studies classrooms; though, research has long shown numerous benefits. This lesson seeks to utilize the inquiry method to invigorate the social studies curriculum as well as explore a controversial topic of gender equality in historic representation. Women are often underrepresented in history textbooks and curriculum. Thus, students may examine various females and their role in history; more specifically this lesson aims to explore women from the 1920s to fight the misconception that women quickly earned equal status as men because of their enfranchisement with the passing of the Nineteenth Amendment.

Human mobility in the context of climate change is often identified as one of the largest future impacts of the climate crisis. It is often assumed by international institutions and national governments that climate change will drive mass migration movements across borders, leading to a prioritization of research that aims to predict future climate migration to aid border security and the creation of migration policies. This article focuses on knowledge production research concerning around climate-related mobility and how knowledge being produced upholds state-centric approaches to migration and migration management. It argues that by leaving state-centric approaches to migration unquestioned in the name of managing climate-related mobility, national governments and other institutions reproduce inequalities for those who are in the nexus of migration and climate change. This article considers alternative conceptions of mobility and climate change, including the climate mobilities paradigm and decolonial understandings of migration, and how these can shift our analytical focus to more holistic and decolonial understandings of migration.

Mentorship is recognized as beneficial to the personal and professional development of physicians. It has been shown to positively influence career success and research productivity for the mentee, while being associated with increased job satisfaction and lower risk of burnout for the mentor. At an institutional level, when aligned with strategic priorities, mentorship can facilitate gender and racial equality, and improve faculty retention. Consequently, there are calls to prioritize and formalize mentorship, yet the optimal way to achieve this remains elusive. How exactly do we create a mentorship program that is viewed as effective from the perspective of the mentor, mentee, and the institution? In this article we approach mentorship as a complex system, and through this lens we aim to provide medical educators and leaders with guidance on how to create and evaluate a program that provides mentees with distributed and precision mentoring, while also aligning with institutional priorities.

Introduction: The incidence of feto-maternal complications is high in women with sickle cell disease. The paucity of high-quality evidence has led to conditional recommendations for transfusional support in pregnant patients. This study aimed to assess if scheduled partial red cell exchanges impact pregnancy outcomes in sickle cell disease patients. Methods: Forty-seven pregnancies were divided into two groups based on whether patients received scheduled partial red cell exchanges. Collected data included demographics, laboratory values, number of hospital visits, and prenatal/perinatal/postnatal outcomes. Data were analyzed using descriptive statistics, t-test, Chi-square and Fisher's exact tests, and binary regression. Results: The mean age was 25.09 ± 4.39 years. Of 47 patients, 14 (29.8%) received scheduled red cell exchanges with 78.6% compliance with no evidence of alloimmunization. This procedure during pregnancy was associated with fewer admissions for pain crises (p=0.032), higher gestational age at delivery (p=0.007), and a lower incidence of neonatal intensive care admissions (p=0.011; odds ratio: 0.071; 95% confidence interval: 0.008-0.632). Logistic regression did not show any significant associations. Conclusions: Sickle cell disease patients with complications in previous pregnancies, including high hospitalization/admission rates and preterm deliveries, could benefit from scheduled partial red cell exchanges or simple transfusions. Further research is needed to guide clinical practice pertaining to transfusional support in pregnant patients with sickle cell disease.

Fahr’s disease (FD), otherwise known as primary familial brain calcification, is a rare neurodegenerative condition that involves intracerebral calcification at the level of the basal ganglia and other brain regions. It is an inherited neurologic disorder, although its molecular genetics have not been thoroughly defined. Patients usually present with a wide range of symptoms, predominantly movement disorders and cognitive changes. However, seizures are a rare initial presenting features of late-onset FD in adults. Herein, we present the case of a 60-year-old man with no known chronic illnesses who was admitted to a tertiary hospital after experiencing first-time generalized tonic-clonic seizures and loss of consciousness for two days. Basic laboratory results were within normal limits, and a non-contrast brain computed tomography (CT) scan showed intracerebral calcification. The patient was diagnosed with epilepsy secondary to FD based on its modified diagnostic criteria and responded well to antiepileptic treatment. The case highlights a rare association and emphasizes the importance of considering this diagnosis in patients experiencing an inaugural seizure; appropriate tests should be performed to confirm or rule out other relevant and secondary causes, and the treatment should be modified accordingly.

While Latinx children are the fastest-growing segment of the U.S. school population, the majority of Latinx Catholic school children may never be instructed or led by a Latinx teacher, principal, or administrator. This is a lamentable gap given that a shared student and teacher identity (i.e., home language, ethnicity, background knowledge, lived experiences) can lead to improved academic outcomes (Dixon, 2017) and non-academic outcomes (Carver-Thomas, 2018), that Latinx educators have conveyed a more profound sense of dedication and belonging when their identity is recognized and valued (Flores et al., 2018), and that there are persistent challenges in the retention of Latinx educators (Ocasio, 2019). To address these gaps, a year-long formation program was developed for Latinx educators and leaders in Catholic schools. Through surveys and interviews from participants in the first cohort, insights and evidence in this pilot study are shared in regard to the impact of the affinity group experience upon empowerment, advancement, and retention of Latinx leadership in Catholic education. Implications discuss how educator and leadership formation programs can support the needs of Latinx educators and leaders in Catholic education.

Objective: To examine experiences of anti-Indigenous racism in a Canadian medical school and inform the development of critical and action-oriented Indigenous health education necessary to pave the way for reconciliation within health systems. Design: A qualitative study conducted within a constructivist paradigm which involved: (1) semi-structured interviews with students, faculty and staff at a Canadian medical school; and (2) consensus-building/collaborative analytical sessions with an Indigenous advisory group and a non-Indigenous working group. Setting: Twenty-three semi-structured interviews were completed with students, staff and faculty working across a Canadian medical school. Results: Inductive coding generated 211 codes that were grouped into seven overarching thematic domains. By engaging in an iterative dialogue with the advisory and working groups, we deductively aligned the thematic analysis with faculty-level and institution-level Indigenous education strategies to ensure local relevance. Self-reflective statements were developed with the advisory group to guide areas for action and resulted in 18 statements with five-point Likert-type-style response options. Conclusion: The results of this study suggest that promoting self-reflexivity in health professional education can prompts educators to engage with Indigenous health curriculum and pedagogy; mentorship and role modelling; and accountability. Critically evaluating systemic injustices at an individual level enables educators to resist systemic oppression and create change in the spaces where they work.