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B7-H4 is a negative regulatory B7 family member. We investigated the role of host and donor B7-H4 in regulating acute graft-versus-host disease (GVHD). Allogeneic donor T cells infused into B7-H4-/- versus WT recipients markedly accelerated GVHD-induced lethality. Chimera studies pointed toward B7-H4 expression on host hematopoietic cells as more critical than parenchymal cells in controlling GVHD. Rapid mortality in B7-H4-/- recipients was associated with increased donor T cell expansion, gut T cell homing and loss of intestinal epithelial integrity, increased T effector function (proliferation, proinflammatory cytokines, cytolytic molecules), and reduced apoptosis. Higher metabolic demands of rapidly proliferating donor T cells in B7-H4-/- versus WT recipients required multiple metabolic pathways, increased extracellular acidification rates (ECARs) and oxygen consumption rates (OCRs), and increased expression of fuel substrate transporters. During GVHD, B7-H4 expression was upregulated on allogeneic WT donor T cells. B7-H4-/- donor T cells given to WT recipients increased GVHD mortality and had function and biological properties similar to WT T cells from allogeneic B7-H4-/- recipients. Graft-versus-leukemia responses were intact regardless as to whether B7-H4-/- mice were used as hosts or donors. Taken together, these data provide new insights into the negative regulatory processes that control GVHD and provide support for developing therapeutic strategies directed toward the B7-H4 pathway.

There is a growing consensus that the modern food system lies at the centre of the great challenges facing humanity and that urgent and profound changes are required in the way that food is produced, processed, distributed and consumed. This review analyses sustainability transitions within agrifood systems, focusing on the role of firms and industries as defined by the Sustainable Transitions Research Network (STRN). This paper conducts the first systematic literature review using bibliometric analysis to assess the current state of research on this theme. The findings reveal a significant increase in publications related to firms and industries associated with agrifood sustainability transitions. Furthermore, the focus of current research is geographically concentrated in the European Union. The review identifies four key themes in the literature, based on the co-occurrence of keywords. These are agriculture, innovation, governance, food systems and agroecology. The review identifies an increasing awareness of the role of farmers in driving sustainability transitions at the farm level. Furthermore, there is an increasing awareness of the interrelated characteristics of the agrifood system, which acknowledges the need for sustainable innovations to occur at multiple stages of the agrifood system. The review also shows that there is growing evidence that innovations can occur through disruptive as well as incremental innovation and highlights the importance of governance influencing transitions. The existing literature raises questions about alternative food networks as sustainable innovations, their potential for significant change in the established food system and the validity of their claims regarding food equity and environmental sustainability. A key theme emerging from the literature is an ecological perspective that identifies the complex biological processes and ecosystems that form an integral part of agricultural production. These findings provide a greater understanding of the current literature landscape of agrifood sustainable transitions relating to firms and industries and lay a foundation for future research. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a common disorder of pregnancy with short- and long-term consequences for mother and baby. Pre-eclampsia is of major concern to obstetricians due to its sudden onset and increased morbidity and mortality for mother and baby. The incidence of these conditions continues to increase due to widespread maternal obesity. Maternal obesity is a risk factor for GDM and pre-eclampsia, yet our understanding of the role of adipose tissue and adipocyte biology in their aetiology is very limited. In this article, available data on adipose tissue and adipocyte function in healthy and obese pregnancy and how these are altered in GDM and pre-eclampsia are reviewed. Using our understanding of adipose tissue and adipocyte biology in non-pregnant populations, a role for underlying adipocyte dysfunction in the pathological pathways of these conditions is discussed., Author(s): Cara Trivett [sup.1] , Zoe J. Lees [sup.1] , Dilys J. Freeman [sup.1] Author Affiliations: (1) Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK Introduction Maternal [...]

Despite the availability of a number of efficacious treatments for Parkinson's disease, their limitations and drawbacks, particularly related to low brain bioavailability and associated side effects, emphasize the need for alternative and more effective therapeutic approaches. Nanomedicine, the application of nanotechnology in medicine, has received considerable interest in recent years as a method of effectively delivering potentially therapeutic molecules to the brain. In particular, polymeric nanoparticles, constructed from biodegradable polymer, have shown great promise in enhancing therapeutic efficacy, reducing toxicity, and ensuring targeted delivery. However, their clinical translation remains a considerable challenge. This article reviews recent in vitro and in vivo studies using polymeric nanoparticles as drug and gene delivery systems for Parkinson's disease with their challenges and future directions. We are also particularly interested in the technical properties, mechanism, drugs release patterns, and delivery strategies to overcome the blood–brain barrier. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Reduced spontaneous blinking is a recognized Parkinson's disease (PD) feature. In contrast, voluntary blinking has been less studied and might serve as a measurable marker of facial bradykinesia. We tested 31 PD patients and 31 controls. Participants were filmed during conversation and a rapid blinking task. Both tasks were videorecorded to count the number of blinks per second. PD patients had lower blink rates. Rapid blinking accurately discriminated between groups with 77% sensitivity and 71% specificity. To conclude, rapid blinking may be a simple and quantifiable task of facial bradykinesia. Plain Language Summary: Decreased blinking without conscious effort is a well-known characteristic of Parkinson's disease (PD). However, voluntary blinking, which is blinking on purpose, has not been studied as much and could be a sign of slower facial movements. We studied a group of people with PD and another one without the disease. We recorded videos of them talking and doing a task where they blinked quickly. Then, we counted how many times they blinked per second in each video. We found that people with PD blinked less often. The rapid blinking task accurately distinguished between those with PD and those without it, being correct about 77% of the time for spotting PD and 71% for spotting non-PD. In conclusion, the rapid blinking task could be a simple and measurable way to identify slower facial movements in PD. [ABSTRACT FROM AUTHOR]

This article argues that broader, more open and inclusive scientific and educational discourses are necessary to achieve social justice through the provision of public education. Paradoxically, research and policy trends over the last two decades have constituted a "narrowing" of educational focus, educational response, and educational possibilities in many Western countries. Simplistic, adversarial and exclusionary paradigms serve to perpetuate the apparent impotence of public education to address social inequities, and serve only to limit potential collaboration between educators, researchers, policy-makers and other stakeholders in education (not least, students and families themselves). There is a need to step beyond the binaries and oppositions that characterise standardised and monolithic approaches to education and research, to negotiate shared "spaces of inquiry" in order to understand the complexities of schools as dynamic institutional settings, in order to bring about a more effective and equitable public education system.

The South Australian Education Department introduced the School Entry Assessment (SEA) Policy in 2001 to help teachers assess young learners and plan relevant learning events, to help collect information about South Australian education from Pre-School to Year 3, and to facilitate collaboration within and between educational and social institutions. Implementation of the School Entry Assessment (SEA) Policy was supported in a limited number of schools by the School Entry Assessment Mentor Project (SEAMP), which reported generally positive results and concluded that mentoring was an effective way to support new policy implementation. However, the SEA Mentor Project was discontinued in 2005, and it remains unclear how teachers and schools that were not mentored are implementing the School Entry Assessment (SEA) Policy, how they are feeling about its implementation, what training and supports they have received, or how they are using the accompanying documentation. This exploratory qualitative study involved comparative analysis of interview responses from eight Reception teachers currently working in South Australian public (state) schools. It was found that positive attitudes towards the School Entry Assessment (SEA) Policy have not necessarily translated into a thorough policy implementation in some schools; that the practices and attitudes of some teachers may be based on limited understandings about the aims of the School Entry Assessment (SEA) Policy; and that some Reception teachers may not be involving parents and caregivers in their considerations about the policy. It also appears that some teachers believe the School Entry Assessment (SEA) Policy only concerns the first year of school (Reception in South Australia), Data collected for this study lends weight to concerns about the disenfranchisement of teachers and about teachers' workloads, especially concerning non-teaching or administrative expectations, and suggests that more inclusive policy-development processes may engender more commitment to shared goals. The argument is made that new policy must include an adequate budget for initial training and ongoing support to facilitate a successful and thorough policy implementation, and that the savings made in initial expenditure may be a false economy, leading to less efficient long-term use of limited public resources.