Increased ICAM-1 Expression Causes Endothelial Cell Leakiness, Cytoskeletal Reorganization and Junctional Alterations

Tumor necrosis factor (TNF)-induced ICAM-1 in endothelial cells (EC) promotes leukocyte adhesion. Here we report that ICAM-1 also effects EC barrier function. Control- or E-selectin-transduced human dermal microvascular EC (HDMEC) form a barrier to flux of proteins and to passage of current (measured as transendothelial electrical resistance or TEER). HDMEC transduced with ICAM-1 at levels comparable to that induced by TNF show reduced TEER, but do so without overtly changing their cell junctions, cell shape, or cytoskeleton organization. Higher levels of ICAM-1 further reduce TEER, increase F/G-actin ratios, rearrange the actin cytoskeleton to cause cell elongation, and alter junctional zona occludens 1 and vascular endothelial-cadherin staining. Transducing with ICAM-1 lacking an intracellular region also reduces TEER. TNF-induced changes in TEER and shape follow a similar time course as ICAM-1 induction; however, the fall in TEER occurs at lower TNF concentrations. Inhibiting NF-κB activation blocks ICAM-1 induction; TEER reduction, and shape change. Specific small-interfering RNA knockdown of ICAM-1 partially inhibits TNF-induced shape change. We conclude that moderately elevated ICAM-1 expression reduces EC barrier function and that expressing higher levels of ICAM-1 affects cell junctions and the cytoskeleton. Induction of ICAM-1 may contribute to but does not fully account for TNF-induced vascular leak and EC shape change

Proteomic Analysis of Salmonella enterica Serovar Typhimurium Isolated from RAW 264.7 Macrophages

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Of, By, and For Which People? Government and Contested Heritage in the American Midwest

Two government-owned and managed heritage sites in Indiana, USA, offer an opportunity to explore the role of governments in adjudicating the competing paradigms of value and contested uses. Strawtown Koteewi is a Hamilton County park and Mounds State Park is part of the Indiana Department of Natural Resources statewide park system. Each site has come under scrutiny in recent years. Strawtown Koteewi is one of the most significant sites in the area for understanding the history of Native peoples. After almost a decade of archaeological excavations, several Native American groups, under the auspices of the Native American Graves Protection and Repatriation Act (NAGPRA), initiated repatriation processes for the recovery of human remains, and some objected to the ongoing archaeological research. At Mounds State Park a coalition of citizens opposed a planned dam project intended to ensure a safe and plentiful water supply and to spur economic development in the area. In each case, the government entities have had to navigate the political landscapes of competing claims about the sites. These case studies expose the fissures between authorized heritage discourse and the paradigms of meaning among the diverse constituencies of the sites, and they highlight the tenuous position of public governance in privileging competing cultural, economic, and social interests. While not unique, the state and county agencies’ positions within these fields of power and their strategic choices reveal some of the barriers and constraints that limit their actions as well as the deep-seated ideologies of policies that perpetuate settler colonial politics in the control and interpretation of indigenous heritage

Multiple Sclerosis Decreases Explicit Counterfactual Processing and Risk Taking in Decision Making

Deficits in decision making (DM) are commonly associated with prefrontal cortical damage, but may occur with multiple sclerosis (MS). There are no data concerning the impact of MS on tasks evaluating DM under explicit risk, where different emotional and cognitive components can be distinguished.Methods: We assessed 72 relapsing-remitting MS (RRMS) patients with mild to moderate disease and 38 healthy controls in two DM tasks involving risk with explicit rules: (1) The Wheel of Fortune (WOF), which probes the anticipated affects of decisions outcomes on future choices; and (2) The Cambridge Gamble Task (CGT) which measures risk taking. Participants also underwent a neuropsychological and emotional assessment, and skin conductance responses (SCRs) were recorded.Results: In the WOF, RRMS patients showed deficits in integrating positive counterfactual information (p <0.005) and greater risk aversion (p <0.001). They reported less negative affect than controls (disappointment: p = 0.007; regret: p = 0.01), although their implicit emotional reactions as measured by post-choice SCRs did not differ. In the CGT, RRMS patients differed from controls in quality of DM (p = 0.01) and deliberation time (p = 0.0002), the latter difference being correlated with attention scores. Such changes did not result in overall decreases in performance (total gains).Conclusions: The quality of DM under risk was modified by MS in both tasks. The reduction in the expression of disappointment coexisted with an increased risk aversion in the WOF and alexithymia features. These concomitant emotional alterations may have implications for better understanding the components of explicit DM and for the clinical support of MS patients

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

DISTRIBUTION OF COLOR-MARKED GREATER SANDHILL CRANES BANDED IN UTAH

Twenty-eight greater sandhill cranes (Grus canadensis tabida) were banded and color-marked on nesting grounds in northern and central Utah during summers 1986 and 1987. Sixteen were observed 1 or more times between October 1986 and February 1988 on migration, winter and summer areas. Marking studies showed that cranes nesting east and southeast of the Great Salt Lake in northern and central Utah are affiliated with the Rocky Mountain population, with most individuals migrating during the spring and fall through the San Luis Valley, Colorado and wintering in southcentral and southwestern New Mexico, southeastern Arizona and possibly northern Mexico. Future color-marking efforts will be in northwest Utah to determine population affiliation of these cranes