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The Role of Insulin Receptor Isoforms in Health and Disease
No full textThe insulin receptor (IR) is a critical regulator of mammalian metabolic and mitogenic processes. It is expressed as two alternatively spliced isoforms that differ by a 12-amino-acid sequence encoded by exon 11 of the IR gene. Whether there are functional differences between the two isoforms is unknown. While early research suggests that IR isoform B (IR-B) plays a more prominent role in metabolic regulation than IR isoform A (IR-A), direct evidence remains limited due to the dearth of experimental models to assess their native properties in vivo. To address this gap in knowledge, we generated mice lacking IR-A through homologous recombination and mice lacking IR-B with CRISPR/Cas9 editing. We then characterized IR-A-/- and IR-B-/- mice in various pathophysiological conditions.
Young-adult IR-A-/- females showed lower triglyceride (TG) excursion on lipid tolerance test (LTT) and lower glycemic excursion on oral glucose tolerance test (oGTT), while their fat and lean content was preserved. Periodic acid–Schiff (PAS) staining demonstrated lower hepatic glycogen after refeeding, and qPCR analyses revealed differential expression of glycogen metabolism-related genes in liver and gastrocnemius. Hepatic IR phosphorylation was enhanced in refed females. We did not find any significant metabolic differences between male wildtype (WT) and IR-A-/- littermates across all assays.
In contrast, female and male IR-B-/- mice had higher refed plasma TG and larger LTT peaks. These mice also had greater fat mass and lower lean mass, accompanied by reduced fasting non-esterified fatty acids (NEFAs). Female, but not male IR-B-/- exhibited a trend toward lower glucose excursions on oGTT, intraperitoneal (IP) GTT (iGTT), pyruvate tolerance test (PTT), and insulin tolerance test (ITT). Radiolabeled tracer studies revealed increased 14C-oleic acid retention in liver and decreased 3H-triolein in perigonadal adipose tissue (pGAT) of male IR-B-/- mice. Hepatic IR phosphorylation was reduced during refeeding in male IR-B-/- mice. Ligand-binding assays in IR-B-/- livers showed normal insulin affinity but displayed higher IGF-2 affinity. Correspondingly, IR-B-/- females had decreased glucose levels after IP IGF-2 administration and reduced IGF-2–stimulated IR phosphorylation in the livers.
Whole-body adiposity in female and male IR-B-/- mice became markedly greater with age. Aging females also had lower fasting NEFAs and higher fasting glucose. When subjected to a high-fat diet (HFD), male IR-B-/- mice developed impaired fasting glucose and iGTT and PTT responses, with no differences in fat and lean mass between genotypes. Hepatic IR phosphorylation dropped sharply on an oGTT challenge in these mice. Calorie restriction (CR) produced the opposite phenotype: CR–IR-B-/- males showed lower refed glucose and insulin after refeeding, decreased fat and lean composition, and increased fasting NEFAs. IR phosphorylation was decreased in refed livers and gastrocnemius of these mice.
In summary, IR-A deletion impacts lipid and glucose tolerance only in females, whereas IR-B deletion raises postprandial TG under physiological conditions but drives age- and diet-sensitive shifts in glycemia and adiposity. Specifically, body-fat expansion in IR-B-/- mice increases with age, normalizes under diet-induced obesity (DIO), and reverses under CR. Collectively, the data show that IR-A and IR-B have sex- and context-dependent effects on glucose and lipid metabolism, which could, at least in part, be attributed to differential phosphorylation dynamics between the two isoforms
Transcriptional Regulation of Progenitor Cell Fate in Craniofacial Ligament Regeneration
No full textMammalian healing is commonly limited by the formation of a fibrotic scar rather than regeneration via differentiation of native tissue. This is especially true for traumatic ligament injuries, which have lifelong clinical consequences even after surgical reconstruction. Here, we establish the adult zebrafish interopercular-mandibular (IOM) ligament as a novel model capable of scar-free regeneration within a month following transection injury.
Lineage tracing shows that ligament regeneration occurs through de-differentiation and cell cycle re-entry of the ligamentocyte lineage to a regenerative mesenchyme progenitor state. Single-cell RNA sequencing highlights that these cells undergo dynamic transcriptional changes in both fibroblast and immune populations within the first 3 days following injury, and that the regenerative mesenchyme is transcriptionally distinct from the developing ligament.
These transcriptional changes are accompanied by dynamic shifts in chromatin accessibility in regenerating fibroblasts, which show a global increase in AP-1 motif accessibility. Finally, comparison of these sequencing data to other regenerating fibroblasts in tail fin, heart, spinal cord, and whole joint identifies a shared injury-activated fibroblast state. Together, these findings establish the adult zebrafish as a model for scar-free ligament regeneration and suggest that the regenerative capacity of zebrafish relies on fibroblast de-differentiation using a regeneration-specific program
Cervical length of preoperative cervical cerclage prognostic impacted the effect of cervical insufficiency
No full textBackground
This study aimed to analyze the impact of preoperative cervical length before cervical cerclage on the extension of gestational days in patients with various diagnostic types of cervical insufficiency, including obstetric history-based diagnosis, ultrasound-based diagnosis, and physical examination-based diagnosis.
Methods
168 patients were segregated into four categories based on cervical length: 0–0.4 cm, 0.5–1.4 cm, 1.5–2.4 cm, and ≥ 2.5 cm. Kaplan-Meier, linear regression curve and Cox regression analyses were used, with a focus on clinical variables, particularly cervical length and the duration of extension after cervical cerclage.
Results
The length of the cervix prior to cervical cerclage correlated with the prognosis of 168 postoperative patients by linear regression analysis. When delivery beyond 28 or 34 weeks was set as the primary prognostic indicator, univariate Cox analysis showed that postoperative C-reactive protein (CRP) level was identified as a risk factor for gestational age extension in cervical cerclage patients. Longer cervical length was identified as a protective factor for overall gestational age extension in cervical cerclage patients. In addition, the obstetrical-history diagnosis group had a better prognosis compared to the emergency cerclage group, which had a worse prognosis compared to the ultrasound-based diagnosis group. Kaplan-Meier curve analysis of all patients revealed a statistically significant impact of different cervical lengths on the gestational age of delivery (P < 0.001). However, in the physical examination-based diagnosis group, Kaplan-Meier curve analysis demonstrated a statistically significant impact of different cervical lengths on gestational age at delivery (P = 0.006).
Conclusion
Longer preoperative cervical length was associated with better outcomes in terms of gestational prolongation and newborn survival after cervical cerclage
Rosario Agroecological Transition and Green and Just Recovery: Scaling Up Urban and Peri-urban Agriculture
No full textThe city of Rosario is a remarkable example of agroecological food production through urban and peri-urban agriculture (UPA), with a focus on social inclusion, co-production of knowledge, and co-management to ensure equity. Over the years, local policies have evolved to promote the creation of green jobs and an equitable recovery from economic crises, as well as to emphasize the role of agroecology as an ecosystem service and a preventive measure against urban expansion, addressing ongoing debates on climate change.
The Urban Agriculture Program (UAP) and Green Belt Project (GBP) are Rosario's principal agro-ecological initiatives. The UAP was implemented in 2002, while the GBP was implemented in 2016. They prioritize green employment, social equity, and mutual support, while promoting the distribution of healthy food through sustainable methods and technologies, and foster interaction between consumers and producers.
The implementation of the programs has led to the development of a multi-level governance strategy aimed at tackling complex socio-economic-environmental issues. The primary focus is to advance sustainable food production and equity, with consideration given to climate change benefits. This includes enhancing the city's climate resilience, as well as lessening its environmental footprint and greenhouse gas emissions.
Keywords: green jobs, ecosystem services, agro-ecological transitio
Creating Time and Space for the Intersection of Climatological Disasters and Racial Inequalities Curricula in the Classroom
Get PDFRacial disparities and climatological disasters are complex topics rarely addressed in K-12 curricula. Each topic has long been neglected vis-à-vis a pedagogy that has either lagged behind contemporary issues or has intentionally sidestepped the importance of addressing these themes through legal and policy mechanisms that limit educators’ ability to discuss each topic. When it comes to students and communities of color in the U.S. who are unequally vulnerable to and affected by the impacts of climate change, it is a significant disservice not to provide fundamental learning opportunities that allow students to engage and contribute to the discourse surrounding these pressing issues. This project was intended to support educators and administrators in implementing pedagogy around these topics conducive to curriculum standards and explicitly developed content for students in grades 8-12. The research question was, “How can the racial inequalities of disaster vulnerability and recovery be addressed in the classroom effectively to build a comprehensive knowledge base, to educate and empower a generation of students who will experience considerably more climatological disasters in the future?
Other Selves: Critical Self-Portraiture in Cuba during the “Special Period in the Time of Peace,” 1991-1999
No full textThe path of Cuba’s cultural economy and patrimony deviated substantially during the “Special Period in the Time of Peace” (1991-1999), including the collapse of state sponsorship for the arts and the opening of the Cuban economy to foreign investment. This opening was slight but significant. Artists found themselves in a position where their work no longer solely existed as patrimony of the state but as personal methods of success and survival.
My dissertation analyzes how three Black Cuban artists, René Peña, Belkis Ayón, and Elio Rodríguez, engineer and manipulate self-portraiture as a critical tool through which they can explore issues of belonging and place in connection to the Cuban national project. I attest that each artist positions representations of themselves, or their avatars, within their work to examine what it means to be Cuban, Black, and human.
I begin my project by establishing how the figure of the White, hyper-masculine man has served as the ideal Cuban citizen following the revolution and independence. Cuban artists have explored themes of national identity and belonging since the mid-nineteenth century, in many instances reflecting on race and the presence of African descendants in Cuban society. The continued discourse on “racelessness” and the supposed eradication of racism in the country made the potential to be both Black and Cuban impossible. Official discourses on race after the 1959 revolution attempted to erase, and in many senses, whitewash, the historical legacy of racism in Cuba through the expressly public abolishment of discrimination and difference in Cuban society. An attempt to erase all forms of difference, or the visibility of difference, within Cuban society accompanied advances in equal opportunity to jobs, education, and housing for the Black Cuban community after the revolution.
My project focuses on how Peña, Ayón, and Rodriguez contest the long-established hierarchy of race and gender in official cubanía [Cubanness] through visual discourses. I argue that the works of Peña, Ayón, and Rodríguez are not examples of a hybrid, creolized synthesis but instead working products of investigation and play. Considering identity as a process and project always in flux, I contend that these three artists use aesthetic strategies to represent Cubanness and Blackness as not mutually exclusive but simultaneously iterative and dynamic. Considering their artistic practices as performances of Blackness and self, I present these artists as critical interlocutors of the cultural moment.
I argue that Peña, Rodríguez, and Ayón mobilize the Afro-diasporic conception of the self as external and multiple through their avatars as a form of self-fashioning. An avatar functions as a proxy for a person, acting as an extension of their self, traversing locations and discourses otherwise inaccessible to the primary self. Avatars blur the boundaries between the material and the virtual world and muddle the distinctions between subject and object, flesh and body. Peña, Rodríguez, and Ayón create portraits of their “other selves” to assert their subjectivity and personhood in realms that otherwise negate their presence.
Through a close visual analysis of the work created by Peña, Ayón, and Rodríguez, I show how their use of alter-egos elucidates their experiences of the materiality of Blackness and the multiplicity of being. I argue that this is mainly present in the material processes inherent in the print-making and performative productions included in each. For example, in terms of color, Peña and Ayón use black and white critically, manipulating the various gray scales between the two tones to illustrate the many potentialities of cubanía. Rodríguez has interestingly moved into soft sculptural forms of blacks and whites, but the works discussed here use fixed colors to create a humorous play with traditional Cuban aesthetics.
Each artist uses color differently, but through their processes, they imbue their works with a sense of materiality and personhood that is only possible through print. For these artists, the work’s creation becomes a performance of self-definition that parallels the many ways we perform race, nationhood, and belonging
From Belief to Action: How Failure Beliefs Influence Teacher Response to Struggling Students
No full textGiven the potency of belief constructs in impacting how an individual judges, assesses, and evaluates, a central concern in the field of teaching and learning is how teachers’ beliefs influence their instructional behaviors in the classroom and their interactions with their students. An area of teaching beliefs that has gained additional attention in recent years is teacher beliefs related to student failure. There is now rich literature on teacher expectations and attributions of student failure, and how both belief constructs impact instructional choices. Research in both fields falls short, however, in that neither explicitly explored how teachers define student failure. Instead, both fields focus on the teachers’ affective responses to specific researcher-defined student failures. This is a missed opportunity because it ignores the potential impact of teachers’ own definition of student failure on their instructional behaviors and actions.
Using a mixed-methods research approach, I addressed this gap by undertaking the first systematic investigation of how teachers define student failure. First, I present three studies that were conducted to generate insights into how teachers define student failure. Second, I discuss a scale that I developed for the analysis, Teacher Definitions of Student Failure Scale (TDFS), that captures which struggles teachers consider to be student failures. In other words, the scale captures what a given teacher defines as student failures in their classrooms. To my knowledge, such a measure does not exist. I then present a fourth pre-registered study leveraging a repeated-measures design to examine how teachers’ definition of student failure relates to their response to struggling students. Together, these studies (n = 328) served to investigate two overarching research questions: (a) How do in-service high school teachers define student failure? and (b) Do teachers respond to struggling students differently based on how they define student failure
Dividing Trademark Use
No full textThe trademark law of the United States places special emphasis on whether and how a trademark is used in commerce. But over the long history of the Lanham Act—including some less-than-careful drafting by Congress and some aggressive acts of interpretation by the federal courts—the concept of “use” has become complicated and in many ways confused. Two recent Supreme Court cases—Jack Daniel’s Properties, Inc. v. VIP Products LLC and Abitron Austria GmbH v. Hetronic International, Inc.—reflect and in some ways exacerbate that confusion. But the opinions in these cases also expose an interesting property of “use” in trademark law that has not been deeply examined in the caselaw or the academic literature. That property is that the use of a trademark can be divided among multiple agents with respect to a single product or service. The potential for divided use raises issues of secondary responsibility that trademark law has never comprehensively addressed. This Article catalogues the various notions of “use” in trademark law, shows how Jack Daniel’s and Abitron destabilize these notions, and applies principles of secondary responsibility to attempt to reconcile those cases with other contentious areas of trademark doctrine under the framework of divided use
Exploring Childhood Trauma, Race-Related Stress, Racial Socialization, and Symptoms in Black Emerging Adulthood
No full textObjective: Systemic oppression contributes to disproportionate rates of childhood trauma and race-related stress among Black emerging adults, heightening harmful psychological outcomes (Hope et al., 2022; Williams et al., 2010). This study explored how race-related stress infuences the relationship between childhood trauma and internalizing symptoms in Black emerging adults. It also investigated whether racial socialization messages moderated these efects in a three-way interaction. Methods: Black emerging adults (ages 18 – 25) were recruited through academic channels and social media platforms to complete a demographic questionnaire, the Childhood Trauma Questionnaire – Short Form (CTQ), the Index of Race-Related Stress – Brief Version (IRRS-B), the Racial Socialization Questionnaire-teen (RSQ-t), and the Brief Symptom Inventory–18 (BSI-18). Hayes’ PROCESS Model 3 was utilized to test moderated moderation analysis. Results: Analyses comprised 341 Black emerging adults (75.4% women, 31% 18-year-olds). Race-related stress did not moderate the relationship between childhood trauma and internalizing symptoms, B = -0.004, SE = 0.0025, 95% CI [-0.0054, 0.0046]. The overall moderated moderation model was not signifcant, B = 0.00002, SE = 0.0002, 95% CI [-0.0002, 0.0007]. However, higher endorsed childhood trauma and racial socialization messages, in the absence of race-related stress, were associated with increased internalized symptomology, B = 0.0105, SE = .0045, 95% CI = [0.0017, 0.0194]. Conclusions: These fndings highlight the unique ways childhood trauma, race-related stress, and racial socialization messages impact Black emerging adults’ psychological functioning. A higher frequency of endorsed racial socialization messages may amplify distress associated with childhood trauma. Future research should investigate racial socialization competency and coping self-efcacy to better understand racial socialization’s role as a potential protective factor for Black emerging adults facing psychological distress from trauma and stress