Latham & Watkins (United States)

The Anti-Racist Collections Workbook was developed by a team of librarians at the University of Colorado Boulder as an alternative to traditional diversity audits, which often fail to address systemic issues. Recognizing the deep-rooted ideologies of Whiteness in academic libraries, the workbook uses scholar Diane Gusa’s White Institutional Presence framework to critically examine collection practices. It focuses on six areas: cataloging and classification, selecting materials, purchasing materials, approval profiles, weeding, and community engagement. Each section provides questions to challenge existing practices and promote anti-racist collection policies. By interrogating and adjusting traditional practices, the workbook aims to inspire library practitioners to create inclusive, representative collections that better serve all communities, moving beyond superficial representation to address structural inequities in library systems

BAG3 levels are diminished in patients with heart failure and several mutations have been identified to cause dilated cardiomyopathy with cardiac fibrosis. BAG3’s four binding domains are critical to its function to facilitate proteostasis. BAG3’s role has been extensively studied in CMs, where it aids sarcomere protein turnover through chaperone-assisted selective autophagy, through BAG3’s complex with HSP70, HSPB8, and E3 ligase CHIP. However, BAG3 is ubiquitously expressed and its role in non-myocytes has been overlooked. Cardiac fibroblasts are responsible for the excessive matrix deposition leading to fibrosis, mostly through TGF-beta signaling. Previously, we have shown the importance of BAG3 in cardiac fibroblasts through its role in TGF-beta signaling and identified BAG3 to facilitate the degradation of the type II TGF-beta receptor (TGFBR2). As BAG3 does not have inherent E3 activity, this study aimed to identify the specific E3 ligase of TGFBR2 and the binding domains of BAG3 that are crucial to this interaction to gain insight into the effects of the clinical mutations of BAG3. Immunoprecipitation (IP) of endogenous BAG3 in cardiac fibroblasts revealed five E3 ligases as high-confidence interactors of BAG3. To find the specific E3 ligase of TGFBR2, we performed an IP of a V5-tagged TGFBR2 and identified HSP70, HSPB8 and CHIP as binding partners. To delineate the critical domains of BAG3 that impact the TGFBR2 degradation, we overexpressed 3x-FLAG-tagged BAG3 proteins lacking each domain respectively (WW, IPV, PxxP, and BAG) and show that the BAG domain is imperative in TGFBR2 degradation. This has clinical implications for the common DCM-causing E455K mutation in the BAG domain. The ubiquitination of TGFBR2 was decreased upon overexpression of a BAG3 plasmid containing the E455K mutation. Lastly, the drug JG-98, which disrupts the binding of HSP70 to BAG3, was used to show the importance of the HSP70-BAG3 axis in the degradation of TGFBR2. In conclusion, we have uncovered the molecular mechanism of TGFBR2 degradation in cardiac fibroblasts mediated by the BAG3-HSP70-HSPB8 complex, with clinical implications for the loss of BAG3 and several common DCM-causing mutations in the development of cardiac fibrosis.

Previous research has shown that a 5-day course of morphine enhances nociceptive sensitivity and allodynia when given 10 days after chronic constriction injury (CCI) as measured by the Von Frey test, a test where the hindpaw is poked with force (measured in grams) calibrated filament. This increased sensitivity to touch suggests that post trauma morphine makes second order sensory dorsal horn neurons more excitable. Therefore, it is hypothesized that during morphine enhanced allodynia, dorsal horn neurons will be more excitable to nociceptive stimulus. It was found that morphine enhanced allodynia causes more excitable neurons across a larger spatial range of the spinal cord, both rostral-caudal and dorsal-ventral along the dorsal horn. Mechanisms for the increased excitability of the dorsal horn are proposed and explored. These findings add to a robust literature which has detailed the paradoxical pain amplifying effects of morphine. Further, this study predicts that hyperexcitability of pain and touch pathways may occur as a clinically unintended side effect of morphine when administered to treat ongoing neuropathic pain. Lay Summary When working on the body, opioids take effect on various cells- including cells of the nervous system known as Glia. These glial cells produce various inflammatory responses that are typically known to decrease inflammation in the body. However, prior literature has revealed that following an activated state, these cells enter a “primed” form. If a second immunological activation occurs during this primed state, glial cells have been shown to release proteins that actually potentiate the state of pain. This study examines this hypothesis through the context of peripheral nerve injury (modeling injury, surgery, or trauma), followed by an administration of morphine. Using advanced imaging techniques, we are able to visualize exactly what modulators are inducing this potentiated pain response, as well as where in the nervous system these cells are found. Morphine has a potent effect on various aspects of the nervous system which may be alleviated by other treatment routes that focus specifically on the cell type and location that release the molecules that initiate the healing process. By unveiling the details of this mechanism, we can better understand how to treat patients following injury or surgery without inducing a higher pain response that can be caused by a short-term administration of morphine. To see the complete thesis, please visit https://scholar.colorado.edu/concern/undergraduate_honors_theses/0k225c53t.

In many ways, the early twenty-first century is strikingly different from the early twentieth; but in more than few respects, it is radically the same.Wealth inequality and the concentration of corporate power mirror or exceed their peaks in the 1920s, 1 dislocating person from place, fraying social bonds, and destroying prior land stewardship. 2Union participation is stymied at every corner, depressing wages. 3 Authoritarianism is rising around the globe. 4 The "united" states are engaged in a vitriolic cultural battle over how to deal with their bloody history of racialized violence. 5A pandemic has taken millions of lives and exposed global health inequities. 6 And war rages in continental Europe.

In recent years, practitioners, commentators and competition authorities have been facing the question of whether online platforms fit the mould of a typical agent under EU competition law. The stakes are high. If online platforms could be qualified as agents, the obligations imposed on them in relation to the contracts concluded and/or negotiated on behalf of their principal(s) may fall outside Article 101 (1) TFEU. This article wishes to contribute to the debate in two ways. First, it offers an assessment of whether, under existing EU competition law, online platforms can be qualified as agents. Second, it provides a conceptual framework to determine whether the existing rules are fit for purpose. After a brief overview of the relevant case-law, the article finds that, as a matter of current law, online platforms can fall under the definition of agents. However, the article considers that the existing rules should be updated to reflect the disruptive changes brought by the online platforms revolution. The existing rules were conceived at a time when value was created and transferred following the traditional value chain (or pipeline) model. Value flew in a linear way from producers to consumers. Companies are nowadays increasingly shifting from the value chain model to a more complex business model, i.e. the platform model. The platform model re-shaped ordinary competitive dynamics. Under the platform model, value is created through a complex array of interactions among producers, a number of principals, consumers and online platforms. The output is a package of products and services. Online platforms compete with each other, with other market players and sometimes even with their principals. The article finds that these new challenges are not adequately addressed by the EU Guidelines on Vertical Restraints, that should be reviewed accordingly to catch up with the online platforms revolution.

Italy should unilaterally extend maturities for its domestic government securities to facilitate an orderly and streamlined restructuring that provides Italy with necessary debt relief. Italy’s domestic government securities are issued as decrees under a 2003 Consolidated Act (the “Act”). Article 3 of the Act explicitly grants Italy the power to unilaterally extend maturities for all domestic government securities. To exercise this restructuring power, the Ministry of Economy and Finance (the “Ministry”) must issue a framework decree that authorizes the Treasury to unilaterally reprofile Italy’s debt. In 2011, Edelen et al. first proposed that Italy had the authority under its existing laws to unilaterally reprofile its sovereign debt. The following proposal expands upon and updates the Edelen et al. proposal. It demonstrates that the inclusion of the Collective Action Clauses (“CACs”) in some of its bonds does not foreclose the use of Italy’s Article 3 power. The proposal also describes the mechanics by which Italy would exercise its right to extend maturities. Unilaterally extending maturities does not require any retroactive utilization of the local law advantage. Nor does it expose Italy to significant legal risks in its domestic courts or under European treaties and conventions.

1. Aimee Chung, MD* 2. Melissa Deimling, MD† 1. *Department of Medicine-Pediatrics, Duke University Medical Center, Durham, NC 2. †Latham Pediatrics, Community Care Physicians, Latham, NY 1. 1. Yuki N, 2. Hartung HP Guillain-Barre Syndrome. Yuki N, Hartung HP. N Engl J Med. 2012;366(24):2294–2304 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] 2. 1. Hughes RA, 2. Cornblath DR Guillain-Barre Syndrome. Hughes RA, Cornblath DR. Lancet. 2005;366(9497):1653–1666 [OpenUrl][5][CrossRef][6][PubMed][7][Web of Science][8] 3. 1. van Doorn PA, 2. Ruts L, 3. Jacobs BC Clinical Features, Pathogenesis, and Treatment of Guillain-Barre Syndrome. van Doorn PA, Ruts L, Jacobs BC. Lancet Neurol. 2008;7(10):939–950 [OpenUrl][9][CrossRef][10][PubMed][11][Web of Science][12] Guillain-Barre syndrome (GBS) is a peripheral nervous system disorder that presents as a rapidly progressive, ascending, flaccid paralysis with diminished or absent reflexes. The disease is often triggered by an infectious process, and it affects children of all ages. Once considered a single disease, many subtypes have been identified based on the neuronal components involved. Important subtypes to consider include acute inflammatory demyelinating polyradiculoneuropathy, which targets segments of the myelin sheath. Other subtypes include acute motor axonal neuropathy and acute motor and sensory axonal neuropathy, both of which target the neuronal axon. Miller Fisher syndrome (ataxia, areflexia, and ophthalmoplegia) falls under the GBS categorization as well, although it usually involves minimal to no weakness. With the eradication of poliomyelitis in the developed world, GBS is now the most common cause of acute flaccid paralysis in infants and children, although still rare in children younger than 2 years. The incidence in Western countries ranges from 0.89 … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.aulast%253DYuki%26rft.auinit1%253DN.%26rft.volume%253D366%26rft.issue%253D24%26rft.spage%253D2294%26rft.epage%253D2304%26rft.atitle%253DGuillain-Barre%2Bsyndrome.%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMra1114525%26rft_id%253Dinfo%253Apmid%252F22694000%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMra1114525&link_type=DOI [3]: /lookup/external-ref?access_num=22694000&link_type=MED&atom=%2Fpedsinreview%2F39%2F1%2F53.atom [4]: /lookup/external-ref?access_num=000305174100010&link_type=ISI [5]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DHughes%26rft.auinit1%253DR.%2BA.%26rft.volume%253D366%26rft.issue%253D9497%26rft.spage%253D1653%26rft.epage%253D1666%26rft.atitle%253DGuillain-Barre%2Bsyndrome.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252805%252967665-9%26rft_id%253Dinfo%253Apmid%252F16271648%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [6]: /lookup/external-ref?access_num=10.1016/S0140-6736(05)67665-9&link_type=DOI [7]: /lookup/external-ref?access_num=16271648&link_type=MED&atom=%2Fpedsinreview%2F39%2F1%2F53.atom [8]: /lookup/external-ref?access_num=000233047100028&link_type=ISI [9]: {openurl}?query=rft.jtitle%253DLancet.%2BNeurology%26rft.stitle%253DLancet%2BNeurol%26rft.aulast%253Dvan%2BDoorn%26rft.auinit1%253DP.%2BA.%26rft.volume%253D7%26rft.issue%253D10%26rft.spage%253D939%26rft.epage%253D950%26rft.atitle%253DClinical%2Bfeatures%252C%2Bpathogenesis%252C%2Band%2Btreatment%2Bof%2BGuillain-Barre%2Bsyndrome.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS1474-4422%252808%252970215-1%26rft_id%253Dinfo%253Apmid%252F18848313%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [10]: /lookup/external-ref?access_num=10.1016/S1474-4422(08)70215-1&link_type=DOI [11]: /lookup/external-ref?access_num=18848313&link_type=MED&atom=%2Fpedsinreview%2F39%2F1%2F53.atom [12]: /lookup/external-ref?access_num=000259725700017&link_type=ISI