Mapping the interaction of B cell Leukemia 3 (BCL-3) and nuclear factor κB (NF-κB) p50 identifies a BCL-3-mimetic anti-inflammatory peptide

The NF-κB transcriptional response is tightly regulated by a number of processes including the phosphorylation, ubiquitination, and subsequent proteasomal degradation of NF-κB subunits. The IκB family protein BCL-3 stabilizes a NF-κB p50 homodimer·DNA complex through inhibition of p50 ubiquitination. This complex inhibits the binding of the transcriptionally active NF-κB subunits p65 and c-Rel on the promoters of NF-κB target genes and functions to suppress inflammatory gene expression. We have previously shown that the direct interaction between p50 and BCL-3 is required for BCL-3-mediated inhibition of pro-inflammatory gene expression. In this study we have used immobilized peptide array technology to define regions of BCl-3 that mediate interaction with p50 homodimers. Our data show that BCL-3 makes extensive contacts with p50 homodimers and in particular with ankyrin repeats (ANK) 1, 6, and 7, and the N-terminal region of Bcl-3. Using these data we have designed a BCL-3 mimetic peptide based on a region of the ANK1 of BCL-3 that interacts with p50 and shares low sequence similarity with other IκB proteins. When fused to a cargo carrying peptide sequence this BCL-3-derived peptide, but not a mutated peptide, inhibited Toll-like receptor-induced cytokine expression in vitro. The BCL-3 mimetic peptide was also effective in preventing inflammation in vivo in the carrageenan-induced paw edema mouse model. This study demonstrates that therapeutic strategies aimed at mimicking the functional activity of BCL-3 may be effective in the treatment of inflammatory disease

Robotic-assisted laparoscopic donor nephrectomy: Decreasing length of stay

Background: The number of robotic operations performed with the da Vinci Surgical System has increased during the past decade. This system allows for greater maneuverability and control than hand-assisted laparoscopic procedures, resulting in less tissue manipulation and irritation

Role of special coagulation studies for preoperative screening of thrombotic complications in simultaneous pancreas-kidney transplantation

Background: Vascular thrombosis is a well-known complication after simultaneous pancreas-kidney (SPK) transplantation procedures. The role of preoperative special coagulation studies to screen patients at high risk for vascular thrombosis is unclear and not well studied

To Withdraw or Not to Withdraw: Reviewability of an Agency\u27s Withdrawn Proposed Rule

Federal agencies propose thousands of regulations in any given year. The Administrative Procedure Act requires such agencies to follow certain procedures when enacting rules and regulations. However, when an agency proposes a new rule that is purely discretionary—not mandated by Congress—it may withdraw the proposed rule at any point before the rule is finalized. In October 2017, the Centers of Medicare and Medicaid (CMS) withdrew a proposed rule that, if enacted, would have required long-term care facilities to recognize out of state same-sex marriages as a condition of Medicare and Medicaid participation. In its formal withdrawal published in the Federal Register, CMS reasoned that the proposed rule was no longer necessary due to the U.S. Supreme Court decision in Obergefell v. Hodges. This Comment examines the circumstances under which a district court can review an agency’s withdrawal of a discretionary proposed rule. For nearly forty years, the D.C. Circuit has held that withdrawn discretionary rules may be ripe for judicial review if two requirements are met: (1) the withdrawal signals final agency action and (2) the agency created an adequate and precise record pursuant to informal notice-and-comment rulemaking. However, some commentators, notably former Ninth Circuit Judge Alex Kozinski, argue that an agency’s decision to withdraw a proposed rule is wholly discretionary and thus unreviewable in light of the U.S. Supreme Court decision Heckler v. Chaney. This Comment concludes by arguing that judicial review of withdrawn discretionary proposed rules is necessary to prevent arbitrary and capricious agency action. Moreover, despite Judge Kozinski’s concerns, arbitrary and capricious review supplies a reviewing court with the critical tools to review withdrawn discretionary rules

Residential Mobility in the Late Pre-hispanic Osmore Drainage: Isotopic Analyses of Hair from the Estuquiña

I examine, through isotopic analyses, individual and regional interactions in Peru following the collapse of the large polity, Tiwanaku. After its collapse in the 11th century, former territories experienced violent instability, as new communities formed during the Late Intermediate Period, or LIP (1000-1400s AD). I analyze naturally mummified human hair from the later LIP Estuquiña (1250-1470s AD) in the Moquegua Valley of southern Peru to examine patterns of regional mobility in the aftermath of political fragmentation. Reconstructing residential mobility through isotope analyses is methodologically established, and has been instrumental in understanding mobility, exchange, colonization, and regional interactions during Tiwanaku’s height. However, less is known about these processes following the disbursement of individuals and groups of people after the early LIP when instability transitioned into a different form of uncertainty, caused by environmental factors. Using heavy isotope analysis, I test the oral tradition and ethnohistoric accounts of the origins of members of the LIP Estuquiña cultural group, which suggested populations moved from around the southern Lake Titicaca region into the middle Moquegua Valley of Southern Peru during the Late LIP. I analyzed bulk samples of archaeological hair from ten naturally mummified individuals from the site of Estuquiña, located in the middle Moquegua Valley, Peru. I characterized 87Sr/86Sr and 206Pb/204Pb, 207Pb/204Pb, and 208Pb (206,7,8Pb/204Pb for brevity). Additionally, I analyzed ratios of the same isotopes in a subset of individuals (N = 2), using 1cm increments from roughly thirty strands of hair per individual, aligned by the hair follicles. This allowed me to examine incremental variation in isotope ratios during each month or so leading up to death. Hair 87Sr/86Sr and 206,7,8Pb/204Pb results indicate that only one individual, M6-4203, was distinctly from the altiplano, while two more individuals may have also been from outside, but near to, the region. Most individuals appear to have been locals, isotopically speaking, to the middle Moquegua Valley. These data support recent work by Sutter and Sharratt (2019) arguing that the Estuquiña inhabitants were a contiguous population extending back to the Middle Horizon, rather than a replacement community from highland Lupaqa cultures or other far-flung regions

Contesting the Dominant Discourse of Child Sexual Abuse: Sexual Subjects, Agency, and Ethics

Responding to previous scholars’ call to explore the complexities of child sexual abuse (CSA), this article presents narratives of CSA and scrutinizes a binary construction underpinning this discourse of CSA, namely, the positioning of children as powerless and adults as powerful. The narratives belong to three Indonesian young people who have had sexual interactions with adults when they were children. The findings demonstrate how this binary positioning has been both drawn upon and resisted in the ways participants understand their sexual experiences. This article contributes to the existing literature by providing analyses of some vignettes of everyday experiences of how children might be constituted as sexual subjects, including their capability to exercise agency, perform resistance, and negotiate ethics. The implications of the findings are discussed in relation to how the recognition of children as sexual subjects and their sexual agency might be beneficial for parents, educators, and counselors

Contextualising Chinese migration to Africa

Who are ‘the Chinese’ in Africa? Why are they there? As China’s engagement with African countries intensifies, and the size of the Chinese population in Africa increases, these questions have elicited substantial attention. Many attempts to provide answers, especially in the media and popular publications, are problematically based on uninformed stereotypes and undifferentiated notions of ‘the Chinese’, by implication a homogeneous group lacking contextualisation. Seeking to address such characterisations, this paper uses the digital communications of present and prospective Chinese migrants to provide a more nuanced picture of the motivations, preoccupations and migration experiences of private entrepreneurs and state-owned enterprise workers

A facile and green route to terpene derived acrylate and methacrylate monomers and simple free radical polymerisation to yield new renewable polymers and coatings

We present new acrylic monomers derived directly from abundant naturally available terpenes via a facile, green and catalytic approach. These monomers can be polymerised to create new polymers with a wide range of mechanical properties that positions them ideally for application across the commodity and specialty plastics landscape; from packaging, cosmetic and medical, through to composites and coatings. We demonstrate their utility through formation of novel renewable polymer coatings