In southwest Alaska, dominant narratives of subsistence and conservation are concerned predominantly with material relations with fish, with the number of fish that are killed. In Akiak, an Alaska ...Native (Yupiaq) village located along the Kuskokwim River, people's relations with Chinook salmon (Oncorhynchus tshawytscha) extend beyond the material, encompassing also the temporal. In this article, I contend that state and federal fishing regulations enact and extend settler colonial representations of Indigenous disappearance. Framing Yupiaq people's appeals for "a taste of fish" as a temporal matter, I examine how state and federal fishing regulations rupture the temporality in which Yupiaq people's relations with Chinook salmon unfold and threaten people's well-being. By examining the vitality of human-salmon relations through an optic of care, I describe how Yupiaq peoples in Akiak experience the adverse effects of interrupted and postponed relations with Chinook salmon in "confusion" among youth. In turn, I illustrate how people get on with living despite the limits that the present politics of fisheries management place on their ability to take care of each other on their own terms, and in their own time.
In chronic kidney disease (CKD), loss of functional nephrons results in metabolic and mechanical stress in the remaining ones, resulting in further nephron loss. Here we show that Akt2 activation has ...an essential role in podocyte protection after nephron reduction. Glomerulosclerosis and albuminuria were substantially worsened in Akt2(-/-) but not in Akt1(-/-) mice as compared to wild-type mice. Specific deletion of Akt2 or its regulator Rictor in podocytes revealed that Akt2 has an intrinsic function in podocytes. Mechanistically, Akt2 triggers a compensatory program that involves mouse double minute 2 homolog (Mdm2), glycogen synthase kinase 3 (Gsk3) and Rac1. The defective activation of this pathway after nephron reduction leads to apoptosis and foot process effacement of the podocytes. We further show that AKT2 activation by mammalian target of rapamycin complex 2 (mTORC2) is also required for podocyte survival in human CKD. More notably, we elucidate the events underlying the adverse renal effect of sirolimus and provide a criterion for the rational use of this drug. Thus, our results disclose a new function of Akt2 and identify a potential therapeutic target for preserving glomerular function in CKD.
Epidermal growth factor receptor (EGFR) activation and lipocalin-2 (Lcn2) expression are frequently observed in the same pathological contexts, such as cancers or chronic kidney disease (CKD). ...However, the significance of this association is unknown. Here, we describe the role of Lcn2 in regulating EGFR trafficking. We show that Lcn2 increases EGFR cell surface abundance and is required for transforming growth factor α (TGF-α)-induced EGFR recycling to the plasma membrane and sustained activation. Lcn2 binds to the intracellular domain of EGFR in late endosomal compartments and inhibits its lysosomal degradation. Consistently, Lcn2 enhances EGFR-induced cell migration after TGF-α stimulation. In vivo, Lcn2 gene inactivation prevents EGFR recycling to the plasma membrane in an experimental model of CKD. Remarkably, this is associated with a dramatic decrease of renal lesions. Together, our data identify Lcn2 as a key mediator of EGFR trafficking processes. Hence, therapeutic inhibition of Lcn2 may counteract the deleterious effect of EGFR activation.
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•Lipocalin-2 (Lcn2) induces EGFR maintenance to the cell surface•Lcn2 facilitates EGFR recycling upon TGF-α stimulation•Cytosolic Lcn2 binds to EGFR in late endosomal compartments•Lcn2 allows sustained EGFR activation leading to chronic kidney disease onset
Yammine et al. propose lipocalin-2 (Lcn2) as a regulator of EGFR activity. By binding to TGF-α-activated EGFR intracellular domain, cytosolic Lcn2 enhances its recycling to the cell surface. This accounts for EGFR sustained activation leading to chronic kidney disease and makes Lcn2 a potential therapeutic target in this context.
In chronic kidney disease (CKD), proteinuria results in severe tubulointerstitial lesions, which ultimately lead to end-stage renal disease. Here we identify 4-phenylbutyric acid (PBA), a chemical ...chaperone already used in humans, as a novel therapeutic strategy capable to counteract the toxic effect of proteinuria. Mechanistically, we show that albumin induces tubular unfolded protein response via cytosolic calcium rise, which leads to tubular apoptosis by Lipocalin 2 (LCN2) modulation through ATF4. Consistent with the key role of LCN2 in CKD progression, Lcn2 gene inactivation decreases ER stress-induced apoptosis, tubulointerstitial lesions and mortality in proteinuric mice. More importantly, the inhibition of this pathway by PBA protects kidneys from morphological and functional degradation in proteinuric mice. These results are relevant to human CKD, as LCN2 is increased in proteinuric patients. In conclusion, our study identifies a therapeutic strategy susceptible to improve the benefit of RAS inhibitors in proteinuria-induced CKD progression.
A broadband high-gain bi-layer log-periodic dipole array (LPDA) is introduced for conformal load bearing antenna structures (CLASs) applications. Under the proposed scheme, the two layers of the LPDA ...are printed on two separate thin dielectric substrates which are substantially separated from each other. A meander line geometry is adapted to achieve size reduction for the array. The fabricated and tested array easily exceeds more than an octave of gain, pattern, and VSWR bandwidth.
Salmon are intrinsic to health and well-being in Alaska, and sit at the center of myriad social, cultural, and spiritual practices, norms, and values. These practices and values are essential to ...living and being well in many communities in Alaska, but often remain invisible and unaccounted for in management contexts. This paper stems from the collective efforts of a cross-disciplinary, cross-cultural project team brought together as part of the State of Alaska's Salmon and People (SASAP) knowledge synthesis project. In this paper, we assess the sustainability and equity of Alaska salmon systems through a well-being framework. Key objectives include (1) defining and conceptualizing well-being in the context of Alaska salmon systems; (2) developing and assessing well-being indicators for Alaska salmon systems; and (3) evaluating how well-being concepts are currently incorporated into Alaska salmon management and suggesting improvements. We draw on specific examples to evaluate the application of well-being indicators as a tool to more effectively measure and evaluate social considerations, and discuss how to better integrate well-being concepts into governance and management to improve data collection and decision making. As part of this effort, we discuss trends and inequities in Alaska fisheries and communities that impact well-being, and tensions between equality and equity in the context of Alaska salmon management.
An MEMS reconfigurable broadband pixelated patch antenna is introduced for conformal applications, such as in aircrafts or vehicles. The proposed design considers structural fiberglass composite, ...Rohacell foam, structural epoxy, ultrathin graphite fibers, and conductive epoxy to be the materials of choice. A nonconventional method of MEMS switch installation is developed and used, which requires connecting the MEMS chips to the antenna or feed traces using very small amounts of conductive epoxy and then curing the specimen in an oven. The proposed fabrication and assembly process is a low temperature process and is not limited in terms of specimen size. The proposed reconfigurable antenna has three reconfiguration states that allow it to operate from 1.13 to 1.7 GHz with 3-7 dBi gain, excellent radiation patterns, and low cross polarization.
This report examines the feasibility for non-state actors, including terrorist and insurgent groups, to increase their political and/or economic power by deploying a virtual currency (VC) for use in ...regular economic transactions. This report should be of interest to policymakers interested in technology, counterterrorism, and intelligence and law enforcement issues, as well as for VC and cybersecurity researchers.
Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic
. The C5a complement factor and ...its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes
. Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a-C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a-C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19.
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