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Efficient and targeted delivery of therapeutic agents remains a bottleneck in modern medicine. Here, biochemical engineering approaches to advance the repurposing of extracellular vesicles (EVs) as drug delivery vehicles are explored. Targeting ligands such as the sugar GalNAc are displayed on the surface of EVs using a HaloTag‐fused to a protein anchor that is enriched on engineered EVs. These EVs are successfully targeted to human primary hepatocytes. In addition, the authors are able to decorate EVs with an antibody that recognizes a GLP1 cell surface receptor by using an Fc and Fab region binding moiety fused to an anchor protein, and they show that this improves EV targeting to cells that overexpress the receptor. The authors also use two different protein‐engineering approaches to improve the loading of Cre recombinase into the EV lumen and demonstrate that functional Cre protein is delivered into cells in the presence of chloroquine, an endosomal escape enhancer. Lastly, engineered EVs are well tolerated upon intravenous injection into mice without detectable signs of liver toxicity. Collectively, the data show that EVs can be engineered to improve cargo loading and specific cell targeting, which will aid their transformation into tailored drug delivery vehicles. [ABSTRACT FROM AUTHOR]

Cells use noncanonical autophagy, also called conjugation of ATG8 to single membranes (CASM), to label damaged intracellular compartments with ubiquitin‐like ATG8 family proteins in order to signal danger caused by pathogens or toxic compounds. CASM relies on E3 complexes to sense membrane damage, but so far, only the mechanism to activate ATG16L1‐containing E3 complexes, associated with proton gradient loss, has been described. Here, we show that TECPR1‐containing E3 complexes are key mediators of CASM in cells treated with a variety of pharmacological drugs, including clinically relevant nanoparticles, transfection reagents, antihistamines, lysosomotropic compounds, and detergents. Interestingly, TECPR1 retains E3 activity when ATG16L1 CASM activity is obstructed by the Salmonella Typhimurium pathogenicity factor SopF. Mechanistically, TECPR1 is recruited by damage‐induced sphingomyelin (SM) exposure using two DysF domains, resulting in its activation and ATG8 lipidation. In vitro assays using purified human TECPR1‐ATG5‐ATG12 complex show direct activation of its E3 activity by SM, whereas SM has no effect on ATG16L1‐ATG5‐ATG12. We conclude that TECPR1 is a key activator of CASM downstream of SM exposure. Synopsis: TECPR1 utilizes its Dysferlin domains to detect cytosol‐exposed sphingomyelin at sites of membrane damage, which also triggers its E3 activity in CASM. Unlike ATG16L1, TECPR1 activity remains unaffected by the Salmonella Typhimurium factor SopF. TECPR1‐ATG5‐ATG12 is a key E3 complex in CASM response to membrane damage.TECPR1 is recruited by damage‐induced cytosolic sphingomyelin exposure.DysF domains of TECPR1 bind to sphingomyelin and activate its E3 activity.Inhibition of ATG16L1‐mediated CASM by the Salmonella Typhimurium factor SopF does not affect the E3 activity of TECPR1. [ABSTRACT FROM AUTHOR]

During autophagy, cytosolic cargo is sequestered into double-membrane vesicles called autophagosomes. The contributions of specific lipids, such as cholesterol, to the membranes that form the autophagosome, remain to be fully characterized. Here, we demonstrate that short term cholesterol depletion leads to a rapid induction of autophagy and a corresponding increase in autophagy initiation events. We further show that the ER-localized cholesterol transport protein GRAMD1C functions as a negative regulator of starvation-induced autophagy and that both its cholesterol transport VASt domain and membrane binding GRAM domain are required for GRAMD1C-mediated suppression of autophagy initiation. Similar to its yeast orthologue, GRAMD1C associates with mitochondria through its GRAM domain. Cells lacking GRAMD1C or its VASt domain show increased mitochondrial cholesterol levels and mitochondrial oxidative phosphorylation, suggesting that GRAMD1C may facilitate cholesterol transfer at ER-mitochondria contact sites. Finally, we demonstrate that expression of GRAMD family proteins is linked to clear cell renal carcinoma survival, highlighting the pathophysiological relevance of cholesterol transport proteins. The functions of specific lipids in autophagosome biogenesis are not entirely clear. Here, the authors show that the ER protein GRAMD1C, a cholesterol transport protein, suppresses autophagy initiation and has roles in mitochondrial cholesterol homeostasis and respiration. [ABSTRACT FROM AUTHOR]

The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs. Two new endosomolytic small compounds increase delivery of splice-switching oligonucleotides by interfering with their trafficking to the LAMP1-positive endosomal compartments, inducing endosomal membrane rupture and concurrent oligonucleotide escape into the cytosol. [ABSTRACT FROM AUTHOR]

The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remains elusive. Here, we have screened for regulators of PRKN-independent mitophagy using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as regulators of PRKN-independent mitophagy, with both being dispensable for PRKN-dependent mitophagy and starvation-induced autophagy. We demonstrate that the kinase activity of both GAK and PRKCD are required for efficient mitophagy in vitro, that PRKCD is present on mitochondria, and that PRKCD facilitates recruitment of ULK1/ATG13 to early autophagic structures. Importantly, we demonstrate in vivo relevance for both kinases in the regulation of basal mitophagy. Knockdown of GAK homologue (gakh-1) in C. elegans or knockout of PRKCD homologues in zebrafish led to significant inhibition of basal mitophagy, highlighting the evolutionary relevance of these kinases in mitophagy regulation. The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remain elusive. Here the authors use an siRNA library to screen lipid-binding proteins, and identify the kinases GAK and PRKCD as positive regulators of PRKN-independent mitophagy. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the impact of discharge destination on diabetes‐related limb salvage surgery outcomes post‐hospitalisation. This was a single‐centre, observational, descriptive study of 175 subjects with diabetes who underwent limb salvage surgery of a minor foot amputation or wide incision and debridement for an acutely infected diabetic foot ulcer (DFU). Comparisons were made between subjects discharged home vs a skilled nursing facility (SNF) for 12 months postoperatively. Univariate, multivariate, and time‐to‐event analyses were performed. The SNF discharge group (n = 40) had worse outcomes with longer healing time (P =.022), more rehospitalisations requiring a podiatry consult (P =.009), increase of subsequent ipsilateral major lower‐extremity amputation (P =.028), and a higher mortality rate (P =.012) within the 12‐month postoperative period. There was no significant difference between the cohorts in surgically cleared osteomyelitis (P =.8434). The Charlson Comorbidity Index values for those discharged home and those in a short‐term nursing facility were similar (P =.3819; home x¯=5.33 ± 2.84 vs SNF x¯=5.75 ± 2.06). The planned discharge destination after limb salvage surgery among people with an acutely infected DFU should be an added risk factor for healing outcomes. Patients discharged to SNFs experience additional morbidity and mortality compared with patients discharged home post‐hospitalisation. [ABSTRACT FROM AUTHOR]

RNA-based therapies have great potential to treat many undruggable human diseases. However, their efficacy, in particular for mRNA, remains hampered by poor cellular delivery and limited endosomal escape. Development and optimisation of delivery vectors, such as lipid nanoparticles (LNPs), are impeded by limited screening methods to probe the intracellular processing of LNPs in sufficient detail. We have developed a high-throughput imaging-based endosomal escape assay utilising a Galectin-9 reporter and fluorescently labelled mRNA to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. Furthermore, this assay has been integrated within a screening platform for optimisation of lipid nanoparticle formulations. We show that Galectin-9 recruitment is a robust, quantitative reporter of endosomal escape events induced by different mRNA delivery nanoparticles and small molecules. We identify nanoparticles with superior escape properties and demonstrate cell line variances in endosomal escape response, highlighting the need for fine-tuning of delivery formulations for specific applications. Munson et al. develop a high-throughput Galectin-9 reporter based endosomal escape imaging assay to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. By screening various delivery systems, modulators and combinations of nanoparticle components, the authors demonstrate how nanomedicines can be optimized for superior escape properties and efficacy in specific applications. [ABSTRACT FROM AUTHOR]

In this article, co-authors Eagle Shield, Munson, and San Pedro connect with and extend the new vision and direction as guided by Equity & Excellence in Education's new editorial leadership. They do so by first historically framing the distinct differences between assimilative schooling systems and community-based educational resurgence efforts, and then centering Indigenous Knowledges in their stories of resistance and vitalizing efforts with their communities. Relying on collaborative storying whereby conversations are dialogic and reciprocal, the co-authors emphasize personal experiences of the ways educational movements are enacted in their everyday circumstances. Particular emphasis is placed on the way broad movements such as Black Lives Matter and Water is Life are connected to local community-based reforms. Eagle Shield emphasizes the lessons she learned while opening and directing the Mní Wičhóni Nakíčižiŋ Owáyawa (Defenders of the Water School) during the Standing Rock Movement and how those lessons and dreams are continuing to be realized beyond the movement space. Munson details the ways she has been guided by tribal leadership to expand a teacher education program that emphasizes both language vitalization and the centering of tribal knowledges. Listening closely and carefully, San Pedro shares the ways their lessons connect to, extend, and support pedagogical theories and scholarship that forward BIPOC-centered and justice-driven movements. Their stories address the article's central question: What does education look like when it is supported and directed by the dreams, hopes, and aspirations of community leadership? [ABSTRACT FROM AUTHOR]

Inactivation of the endosomal sorting complex required for transport (ESCRT) machinery has been reported to cause autophagic defects, but the exact functions of ESCRT proteins in macroautophagy/autophagy remain incompletely understood. Using live-cell fluorescence microscopy we found that the filament-forming ESCRT-III subunit CHMP4B was recruited transiently to nascent autophagosomes during starvation-induced autophagy and mitophagy, with residence times of about 1 and 2 min, respectively. Correlative light microscopy and electron tomography revealed CHMP4B recruitment at a late step in mitophagosome formation. The autophagosomal dwell time of CHMP4B was strongly increased by depletion of the regulatory ESCRT-III subunit CHMP2A. Using a novel optogenetic closure assay we observed that depletion of CHMP2A inhibited phagophore sealing during mitophagy. Consistent with this, depletion of CHMP2A and other ESCRT-III subunits inhibited both PRKN/PARKIN-dependent and -independent mitophagy. We conclude that the ESCRT machinery mediates phagophore closure, and that this is essential for mitophagic flux. Abbreviations: BSA: bovine serum albumin; CHMP: chromatin-modifying protein; CLEM: correlative light and electron microscopy; EGFP: enhanced green fluorescent protein; ESCRT: endosomal sorting complex required for transport; HEPES: 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid; HRP: horseradish peroxidase; ILV: intralumenal vesicle; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; LOV2: light oxygen voltage 2; MLS: mitochondrial localization sequence; MT-CO2: mitochondrially encoded cytochrome c oxidase II; O+A: oligomycin and antimycin A; PBS: phosphate-buffered saline; PIPES: piperazine-N,N-bis(2-ethanesulfonic acid); PRKN/PARKIN: parkin RBR E3 ubiquitin protein ligase; RAB: RAS-related in brain; SD: standard deviation; SEM: standard error of the mean; TOMM20: TOMM20: translocase of outer mitochondrial membrane 20; VCL: vinculin; VPS4: vacuolar protein sorting protein 4; Zdk1: Zdark 1; TUBG: Tubulin gamma chain [ABSTRACT FROM AUTHOR]

The removal of mitochondria in a programmed or stress-induced manner is essential for maintaining cellular homeostasis. To date, much research has focused upon stress-induced mitophagy that is largely regulated by the E3 ligase PRKN, with limited insight into the mechanisms regulating basal "housekeeping" mitophagy levels in different model organisms. Using iron chelation as an inducer of PRKN-independent mitophagy, we recently screened an siRNA library of lipid-binding proteins and determined that two kinases, GAK and PRKCD, act as positive regulators of PRKN-independent mitophagy. We demonstrate that PRKCD is localized to mitochondria and regulates recruitment of ULK1-ATG13 upon induction of mitophagy. GAK activity, by contrast, modifies the mitochondrial network and lysosomal morphology that compromise efficient transport of mitochondria for degradation. Impairment of either kinase in vivo blocks basal mitophagy, demonstrating the biological relevance of our findings. Abbreviations: CCCP: carbonyl cyanide-m-chlorophenyl hydrazone; DFP: deferiprone; GAK: cyclin G associated kinase; HIF1A: hypoxia inducible factor 1 subunit alpha; PRKC/PKC: protein kinase C; PRKCD: protein kinase C delta; PRKN: parkin RBR E3 ubiquitin protein ligase. [ABSTRACT FROM AUTHOR]

This article will examine and respond to significant critiques of Indigenous research methodologies as part of an Indigenous Methodologies in Educational Research course at a midsized public university in the intermountain west. The authors will present their perspectives in response to critiques of Indigenous research methodologies as presented at the American Indigenous Research Association’s annual meeting in October of 2014. This collection of responses is offered in an effort to facilitate an interactive dialogue with scholars who use Indigenous research methodologies applicable to multiple fields of study, support scholarship that is responsive to the needs of Indigenous communities, and ultimately center relevant research design and findings within Indigenous paradigms. [ABSTRACT FROM AUTHOR]

Abstract: Trafficking of mammalian ATG9A between the Golgi apparatus, endosomes and peripheral ATG9A compartments is important for autophagosome biogenesis. Here, we show that the membrane remodelling protein SNX18, previously identified as a positive regulator of autophagy, regulates ATG9A trafficking from recycling endosomes. ATG9A is recruited to SNX18‐induced tubules generated from recycling endosomes and accumulates in juxtanuclear recycling endosomes in cells lacking SNX18. Binding of SNX18 to Dynamin‐2 is important for ATG9A trafficking from recycling endosomes and for formation of ATG16L1‐ and WIPI2‐positive autophagosome precursor membranes. We propose a model where upon autophagy induction, SNX18 recruits Dynamin‐2 to induce budding of ATG9A and ATG16L1 containing membranes from recycling endosomes that traffic to sites of autophagosome formation. [ABSTRACT FROM AUTHOR]

In an academic system that perpetuates the control and limitation of Indigenous narrative in order to reinforce the Western settler-colonial framework, Francis and Munson aim to create a more appropriate space for Indigenous scholarship. Through conversation, the authors discuss the exploration of sovereign scholar activism through an Indigenous autoethnographic approach. Tribalography, Survivance, and creation and experiential stories of home serve as fuel for the examination of identity, community, and authenticity in the formation of a framework built upon the scholarship of Indigenous researchers, conversations, and experiences since time immemorial. Questions are posed to continue and broaden the conversation toward actualizing a state of sovereign scholarship and the entrenchment of Tribalography and Survivance as means of establishing an Indigenous scholarship free from the confines of settler-colonialism. [ABSTRACT FROM PUBLISHER]

The espoused foundation of U.S. society, E pluribus unum (out of many, one), is based on the belief that this nation should simultaneously support pluralism and promote unity. The road to making this ideal a reality, however, has not always been smooth. The ever-widening achievement gap highlights how this discordance plays out in our education system. Ethnic studies came about to counterbalance the predominance of Euro-American perspectives in our textbooks and curricula and address the inaccuracies, myths, and misconceptions surrounding other groups. Efforts to create a better and more just America were recently tested, however, when an Arizona law prohibiting school districts from offering courses taught from a specific racial/ethnic perspective targeted the Mexican-American Studies Program in Tucson schools. In contrast, Montana's educators who embrace the Indian Education for All initiative and teach all students about Montana's first inhabitants is thriving. In this article, we summarize the research on ethnic studies; track the inception, opposition, and abolition of the ethnic studies program in Tucson; and describe how Montana legislators, state education agencies, tribal members, and classroom teachers have collaborated and successfully promoted the unprecedented reform effort known as Indian Education for All in this anti-ethnic studies national climate. [ABSTRACT FROM AUTHOR]

Lysosomes are essential organelles that function to degrade and recycle unwanted, damaged and toxic biological components. Lysosomes also act as signalling platforms in activating the nutrient-sensing kinase mTOR. mTOR regulates cellular growth, but it also helps to maintain lysosome identity by initiating lysosomal tubulation through a process termed autophagosome-lysosome reformation ( ALR). Here we identify a lysosomal pool of phosphatidylinositol 3-phosphate that, when depleted by specific inhibition of the class III phosphoinositide 3-kinase VPS34, results in prolonged lysosomal tubulation. This tubulation requires mTOR activity, and we identified two direct mTOR phosphorylation sites on UVRAG (S550 and S571) that activate VPS34. Loss of these phosphorylation sites reduced VPS34 lipid kinase activity and resulted in an increase in number and length of lysosomal tubules. In cells in which phosphorylation at these UVRAG sites is disrupted, the result of impaired lysosomal tubulation alongside ALR activation is massive cell death. Our data imply that ALR is critical for cell survival under nutrient stress and that VPS34 is an essential regulatory element in this process. [ABSTRACT FROM AUTHOR]

The mammalian or mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a ubiquitously expressed multimeric protein kinase complex that integrates nutrient and growth factor signals for the co-ordinated regulation of cellular metabolism and cell growth. Herein, we demonstrate that suppressing the cellular activity of glycogen synthase kinase-3 (GSK3), by use of pharmacological inhibitors or shRNA-mediated gene silencing, results in substantial reduction in amino acid (AA)-regulated mTORC1-directed signalling, as assessed by phosphorylation of multiple downstream mTORC1 targets. We show that GSK3 regulates mTORC1 activity through its ability to phosphorylate the mTOR-associated scaffold protein raptor (regulatory-associated protein of mTOR) on Ser859. We further demonstrate that either GSK3 inhibition or expression of a S859A mutated raptor leads to reduced interaction between mTOR and raptor and under these circumstances, irrespective of AA availability, there is a consequential loss in phosphorylation of mTOR substrates, such as p70S6K1 (ribosomal S6 kinase 1) and uncoordinated-51-like kinase (ULK1), which results in increased autophagic flux and reduced cellular proliferation. [ABSTRACT FROM AUTHOR]

The Vps34 (vacuolar protein sorting 34) class III PI3K (phosphoinositide 3-kinase) phosphorylates PtdIns (phosphatidylinositol) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX (phox homology) and FYVE domains. In the present study, we describe a highly selective and potent inhibitor of Vps34, termed VPS34-IN1, that inhibits Vps34 with 25 nM IC50 in vitro, but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of class I as well as class II PI3Ks. Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)Pbinding probe from endosome membranes, within 1 min, without affecting the ability of class I PI3K to regulate Akt. Moreover, we explored whether SGK3 (serum- and glucocorticoid-regulated kinase-3), the only protein kinase known to interact specifically with PtdIns(3)P via its N-terminal PX domain, might be controlled by Vps34. Mutations disrupting PtdIns(3)P binding ablated SGK3 kinase activity by suppressing phosphorylation of the T-loop [PDK1 (phosphoinositide-dependent kinase 1) site] and hydrophobic motif (mammalian target of rapamycin site) residues. VPS34-IN1 induced a rapid ~50-60% loss of SGK3 phosphorylation within 1 min. VPS34-IN1 did not inhibit activity of the SGK2 isoform that does not possess a PtdIns(3)P-binding PX domain. Furthermore, class I PI3K inhibitors (GDC-0941 and BKM120) that do not inhibit Vps34 suppressed SGK3 activity by ~40%. Combining VPS34-IN1 and GDC-0941 reduced SGK3 activity ~80-90%. These data suggest SGK3 phosphorylation and hence activity is controlled by two pools of PtdIns(3)P. The first is produced through phosphorylation of PtdIns by Vps34 at the endosome. The second is due to the conversion of class I PI3K product, PtdIns(3,4,5)P3 into PtdIns(3)P, via the sequential actions of the PtdIns 5-phosphatases [SHIP1/2 (Src homology 2-domain-containing inositol phosphatase 1/2)] and PtdIns 4-phosphatase [INPP4B (inositol polyphosphate 4- phosphatase type II)]. VPS34-IN1 will be a useful probe to delineate physiological roles of the Vps34. Monitoring SGK3 phosphorylation and activity could be employed as a biomarker of Vps34 activity, in an analogous manner by which Akt is used to probe cellular class I PI3K activity. Combining class I (GDC-0941) and class III (VPS34-IN1) PI3K inhibitors could be used as a strategy to better analyse the roles and regulation of the elusive class II PI3K. [ABSTRACT FROM AUTHOR]

Introduction. Charcot foot is a rare and devastating complication of diabetes. While some risk factors are known, debate continues regarding etiology. Elucidating other associated disorders and their temporal occurrence could lead to a better understanding of its pathogenesis. We applied a large data mining approach to Charcot foot for elucidating novel associations. Methods. We conducted an association analysis using ICD-9 diagnosis codes for every patient in our health system (n = 1.6 million with 41.2 million time-stamped ICD-9 codes). For the current analysis, we focused on the 388 patients with Charcot foot (ICD-9 713.5). Results. We found 710 associations, 676 (95.2%) of which had a P value for the association less than 1.0x10-5 and 603 (84.9%) of which had an odds ratio > 5.0. There were 111 (15.6%) associations with a significant temporal relationship (P < 1.0 x 10-3).The three novel associations with the strongest temporal component were cardiac dysrhythmia, pulmonary eosinophilia, and volume depletion disorder. Conclusion. We identified novel associations with Charcot foot in the context of pathogenesis models that include neurotrophic, neurovascular, and microtraumatic factors mediated through inflammatory cytokines. Future work should focus on confirmatory analyses. These novel areas of investigation could lead to prevention or earlier diagnosis. [ABSTRACT FROM AUTHOR]

Montana's constitutional commitment to the cultural heritages of American Indians exemplifies the practical application of multicultural education. In this article, the authors explore the goals and evolution of Indian Education for All within a multicultural education framework, and discuss how educators are best prepared to implement this transformative educational policy. [ABSTRACT FROM AUTHOR]

Relatively little is known about the lives of transgender people once they are through their gender transition. Even less is known about transgender elders, either those who transitioned many decades ago and now have grown older or those who are transitioning in mid- or later-life. This article reports on the findings of three online surveys of transgender adults age 50 years and older on three topics: sexual violence, elder abuse, and sexuality. Sexual violence and elder abuse had been experienced by a strong majority of those surveyed. The sexuality survey demonstrated clearly that there is a vast range of diversity in transgender people's sexual lives and that the majority of midlife and older transgender people believed their gender identity influenced their sexuality. [ABSTRACT FROM AUTHOR]

Reviews three market theories for stock market valuations in the U.S. Earnings growth theory; Declining equity risk premium theory; Participation of stock investors in a stock market bubble.

Focuses on the intraorganizational aspects of environmental planning behavior. Premise that a planning agency which can coordinate the actions of parallel agencies with direct implementation powers has made a great step towards effective action; Study of planning behavior at the municipal level; Implications for the design of state agencies.

Milwaukee's FORGE was funded by the U.S. Office on Violence Against Women to address a deficit in training and resources on transgender issues, especially the aftereffects of trauma and violence directed toward transgender individuals. FORGE created Transgender Aging Network to connect researchers, service providers, and others to transgender aging-specific topics. [ABSTRACT FROM AUTHOR]