Search

Abstract Van der Waals (vdW) ferroelectrics have attracted significant attention for their potential in next-generation nano-electronics. Two-dimensional (2D) group-IV monochalcogenides have emerged as a promising candidate due to their strong room temperature in-plane polarization down to a monolayer limit. However, their polarization is strongly coupled with the lattice strain and stacking orders, which impact their electronic properties. Here, we utilize four-dimensional scanning transmission electron microscopy (4D-STEM) to simultaneously probe the in-plane strain and out-of-plane stacking in vdW SnSe. Specifically, we observe large lattice strain up to 4% with a gradient across ~50 nm to compensate lattice mismatch at domain walls, mitigating defects initiation. Additionally, we discover the unusual ferroelectric-to-antiferroelectric domain walls stabilized by vdW force and may lead to anisotropic nonlinear optical responses. Our findings provide a comprehensive understanding of in-plane and out-of-plane structures affecting domain properties in vdW SnSe, laying the foundation for domain wall engineering in vdW ferroelectrics.

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.

What is understood as “healing” is often culturally and socially embedded. One’s culture helps to define what it means to be well or unwell, and what it means to heal or recover. Sometimes, one’s culture sits in contrast to the mainstream, western scientific approach to health, often seen as the freedom from illness. A Métis worldview is holistic in itself, and it incorporates notions and practices of well-being that go beyond just being “illness or problem free”. Wellbeing is often directly linked to our relationship with the food that sustains us, to the various animal and plant worlds, to the elements, and to being in “right relationship” to the world and others. Dr. Catherine Richardson Kinewesquao presents an approach to healing which she refers to as transformative, energetic and spiritual. She draws from Cree teachings related to “mamatowisowin”, the life force inherent in all beings and the act of calling forth this energy into the healing process. This life force is connected to dignity, justice and care. Metaphorically, it can be talked about as being released or made available when an individual opens to discussing/facing fears and sorrows, distressing events and losses, and to finding a way to integrate them into their whole being. It is a form of energy transmutation, of becoming more emotionally fluid and liberated from the negativity of what is “acting upon them”. When energy is unblocked or released, particularly in the presence of a compassionate listener, the person may then have more energy for their chosen life projects. By using a response-based approach in the aftermath of violence and degradation, and by contextualizing events through exploratory conversations, one may transform stress into productive energy to fuel life, growth and action. Kinewesquao articulates the use of cultural processes for stress management and working with the natural world to enhance well-being. Ultimately, she makes a case that “positive social responses” (e.g., love, care, compassionate listening, support and cultural rituals) to one’s suffering can be some of the best healing medicines.

[This corrects the article DOI: 10.1371/journal.pone.0176599.].

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.

The nêhiyawêwin (Plains Cree language) Cree word, miskâsowin, relates to the sacred teachings of Treaty Elders of Saskatchewan as a concept pertaining to wellness of “finding one’s sense of belonging”—a process integral in the aftermath of colonial disruption. Métis educator and performance artist Moe Clark offers an approach to healing and well-being, which is imparted through movement, flux and through musical and performance-based engagement. Moe works with tools of embodiment in performance and circle work contexts, including song creation, collaborative performance, participatory youth expression and land-based projects as healing art. She shares her process for re-animating these relationships to land, human kin, and other-than-human kin through breath-work, creative practice and relationality as part of a path to wholeness. The authors document Moe’s approach to supporting the identity, growth, healing and transformation of others.

Abstract Boston Children’s Hospital has established a genomic sequencing and analysis research initiative to improve clinical care for pediatric rare disease patients. Through the Children’s Rare Disease Collaborative (CRDC), the hospital offers CLIA-grade exome and genome sequencing, along with other sequencing types, to patients enrolled in specialized rare disease research studies. The data, consented for broad research use, are harmonized and analyzed with CRDC-supported variant interpretation tools. Since its launch, 66 investigators representing 26 divisions and 45 phenotype-based cohorts have joined the CRDC. These studies enrolled 4653 families, with 35% of analyzed cases having a finding either confirmed or under further investigation. This accessible and harmonized genomics platform also supports additional institutional data collections, research and clinical, and now encompasses 13,800+ patients and their families. This has fostered new research projects and collaborations, increased genetic diagnoses and accelerated innovative research via integration of genomics research with clinical care.

Abstract Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability. We identify key challenges and propose that future works need to leverage idealized systems, known biology and even previously identified epistatic interactions, in order to guide the search for new interactions.

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.

A small molecule which specifically blocks the interaction of Rictor and mTOR was identified utilizing a high-throughput yeast two-hybrid screen and evaluated as a potential inhibitor of mTORC2 activity in glioblastoma multiforme (GBM). In vitro, CID613034 inhibited mTORC2 kinase activity at submicromolar concentrations and in cellular assays specifically inhibited phosphorylation of mTORC2 substrates, including AKT (Ser-473), NDRG1 (Thr-346) and PKCα (Ser-657), while having no appreciable effects on the phosphorylation status of the mTORC1 substrate S6K (Thr-389) or mTORC1-dependent negative feedback loops. CID613034 demonstrated significant inhibitory effects on cell growth, motility and invasiveness in GBM cell lines and sensitivity correlated with relative Rictor or SIN1 expression. Structure-activity relationship analyses afforded an inhibitor, JR-AB2-011, with improved anti-GBM properties and blocked mTORC2 signaling and Rictor association with mTOR at lower effective concentrations. In GBM xenograft studies, JR-AB2-011 demonstrated significant anti-tumor properties. These data support mTORC2 as a viable therapeutic target in GBM and suggest that targeting protein-protein interactions critical for mTORC2 function is an effective strategy to achieve therapeutic responses.

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.

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.