Pathophysiology of aniridia-associated keratopathy: Developmental aspects and unanswered questions

Aniridia, a rare congenital disease, is often characterized by a progressive, pronounced limbal insufficiency and ocular surface pathology termed aniridia-associated keratopathy (AAK). Due to the characteristics of AAK and its bilateral nature, clinical management is challenging and complicated by the multiple coexisting ocular and systemic morbidities in aniridia. Although it is primarily assumed that AAK originates from a congenital limbal stem cell deficiency, in recent years AAK and its pathogenesis has been questioned in the light of new evidence and a refined understanding of ocular development and the biology of limbal stem cells (LSCs) and their niche. Here, by consolidating and comparing the latest clinical and preclinical evidence, we discuss key unanswered questions regarding ocular developmental aspects crucial to AAK. We also highlight hypotheses on the potential role of LSCs and the ocular surface microenvironment in AAK. The insights thus gained lead to a greater appreciation for the role of developmental and cellular processes in the emergence of AAK. They also highlight areas for future research to enable a deeper understanding of aniridia, and thereby the potential to develop new treatments for this rare but blinding ocular surface disease

Chromatin remodeling enzyme Brg1 is required for mouse lens fiber cell terminal differentiation and its denucleation

These studies demonstrate a cell-autonomous role for Brg1 in lens fiber cell terminal differentiation and identified DNase IIβ as a potential direct target of SWI/SNF complexes. Brg1 is directly or indirectly involved in processes that degrade lens fiber cell chromatin. The presence of nuclei and other organelles generates scattered light incompatible with the optical requirements for the lens

Histone posttranslational modifications and cell fate determination: Lens induction requires the lysine acetyltransferases CBP and p300

Lens induction is a classical embryologic model to study cell fate determination. It has been proposed earlier that specific changes in core histone modifications accompany the process of cell fate specification and determination. The lysine acetyltransferases CBP and p300 function as principal enzymes that modify core histones to facilitate specific gene expression. Herein, we performed conditional inactivation of both CBP and p300 in the ectodermal cells that give rise to the lens placode. Inactivation of both CBP and p300 resulted in the dramatic discontinuation of all aspects of lens specification and organogenesis, resulting in aphakia. The CBP/p300(−/−) ectodermal cells are viable and not prone to apoptosis. These cells showed reduced expression of Six3 and Sox2, while expression of Pax6 was not upregulated, indicating discontinuation of lens induction. Consequently, expression of αB- and αA-crystallins was not initiated. Mutant ectoderm exhibited markedly reduced levels of histone H3 K18 and K27 acetylation, subtly increased H3 K27me3 and unaltered overall levels of H3 K9ac and H3 K4me3. Our data demonstrate that CBP and p300 are required to establish lens cell-type identity during lens induction, and suggest that posttranslational histone modifications are integral to normal cell fate determination in the mammalian lens

Standardization of shape memory alloy test methods toward certification of aerospace applications

The response of shape memory alloy (SMA) components employed as actuators has enabled a number of adaptable aero-structural solutions. However, there are currently no industry or government-accepted standardized test methods for SMA materials when used as actuators and their transition to commercialization and production has been hindered. This brief fast track communication introduces to the community a recently initiated collaborative and pre-competitive SMA specification and standardization effort that is expected to deliver the first ever regulatory agency-accepted material specification and test standards for SMA as employed as actuators for commercial and military aviation applications. In the first phase of this effort, described herein, the team is working to review past efforts and deliver a set of agreed-upon properties to be included in future material certification specifications as well as the associated experiments needed to obtain them in a consistent manner. Essential for the success of this project is the participation and input from a number of organizations and individuals, including engineers and designers working in materials and processing development, application design, SMA component fabrication, and testing at the material, component, and system level. Going forward, strong consensus among this diverse body of participants and the SMA research community at large is needed to advance standardization concepts for universal adoption by the greater aerospace community and especially regulatory bodies. It is expected that the development and release of public standards will be done in collaboration with an established standards development organization

Subtle activism: Heterotopic principles for unsettling contemporary academia from within

Research on academic activism tends to foreground vociferous and explicit forms of activism that pursue predefined political agendas. Against this backdrop, this article proposes that academic activism can take more subtle forms. Writing as an academic activist collective, we unpack what subtle activism might look like within the context of contemporary academia. We use Foucault’s concept of heterotopia to argue that subtle activism can expand the space of what is possible in academia today by experimenting with quietly unsettling norms rather than overtly opposing or rejecting them. We offer a set of principles that might underpin a subtle activist agenda, extrapolated from practices from colleagues and from own activist collective. We hope that these principles may serve to inspire other academics wishing to engage in subtle activism by unsettling everyday practices that discreetly challenge the status quo, thereby contributing to gently shifting the agenda for how it is possible to conduct intellectual work in the contemporary neoliberal university context

Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin

OBJECTIVE—Diabetes results from a deficiency of functional β-cells due to both an increase in β-cell death and an inhibition of β-cell replication. The molecular mechanisms responsible for these effects in susceptible individuals are mostly unknown. The objective of this study was to determine whether a gene critical for cell division and cell survival in cancer cells, survivin, might also be important for β-cells