Expression of recombinant human ceruloplasmin – an absolute requirement for splicing signals in the expression cassette

AbstractWe report the successful expression of recombinant human ceruloplasmin which was made possible by inclusion of splicing signals in the expression vector. Ceruloplasmin cDNA expressed from the vector pNUT in baby hamster kidney cells gave protein yields of 0.03 mg/l which increased to 15 mg/l with splicing signals present. The defect in expression from the intronless cDNA is due to complete retention of ceruloplasmin mRNA in cell nuclei. The block to cytoplasmic export is alleviated by splicing signals, allowing full expression of the mRNA

Cornucopia: Temporal safety for CHERI heaps

Use-after-free violations of temporal memory safety continue to plague software systems, underpinning many high-impact exploits. The CHERI capability system shows great promise in achieving C and C++ language spatial memory safety, preventing out-of-bounds accesses. Enforcing language-level temporal safety on CHERI requires capability revocation, traditionally achieved either via table lookups (avoided for performance in the CHERI design) or by identifying capabilities in memory to revoke them (similar to a garbage-collector sweep). CHERIvoke, a prior feasibility study, suggested that CHERI’s tagged capabilities could make this latter strategy viable, but modeled only architectural limits and did not consider the full implementation or evaluation of the approach. Cornucopia is a lightweight capability revocation system for CHERI that implements non-probabilistic C/C++ temporal memory safety for standard heap allocations. It extends the CheriBSD virtual-memory subsystem to track capability flow through memory and provides a concurrent kernel-resident revocation service that is amenable to multi-processor and hardware acceleration. We demonstrate an average overhead of less than 2% and a worst-case of 8.9% for concurrent revocation on compatible SPEC CPU2006 benchmarks on a multi-core CHERI CPU on FPGA, and we validate Cornucopia against the Juliet test suite’s corpus of temporally unsafe programs. We test its compatibility with a large corpus of C programs by using a revoking allocator as the system allocator while booting multi-user CheriBSD. Cornucopia is a viable strategy for always-on temporal heap memory safety, suitable for production environments.This work was supported by the Defense Advanced Research Projects Agency (DARPA) and the Air Force Research Laboratory (AFRL), under contracts FA8750-10-C-0237 (“CTSRD”) and HR0011-18-C-0016 (“ECATS”). We also acknowledge the EPSRC REMS Programme Grant (EP/K008528/1), the ABP Grant (EP/P020011/1), the ERC ELVER Advanced Grant (789108), the Gates Cambridge Trust, Arm Limited, HP Enterprise, and Google, Inc

Isoflavone metabolism in domestic cats (Felis catus): comparison of plasma metabolites detected after ingestion of two different dietary forms of genistein and daidzein

Some felid diets contain isoflavones but the metabolic capacity of cats toward isoflavones is relatively unknown, despite the understanding that isoflavones have divergent biological potential according to their metabolite end products. The objective of this study was to determine the plasma metabolites detectable in domestic cats after exposure to 2 different dietary forms of isoflavones, either as a soy extract tablet ( n = 6) or as part of a dietary matrix ( n = 4). Serial blood samples were collected after isoflavone exposure to identify the plasma metabolites of each cat. Genistein was detected in its unconjugated form or as a monosulfate. Daidzein was detected as both a mono- and disulfate as well as in its unconjugated form. Other daidzein metabolites detected included equol mono- and disulfate, dihydrodaidzein, and O -desmethylangolensin. No β -glucuronide metabolites of either isoflavone were detected. Equol was produced in markedly fewer cats after ingestion of a soy extract tablet as a single oral bolus compared with cats consuming an isoflavone-containing diet. The detectable metabolites of the isoflavones, genistein and daidzein, in domestic cat plasma after dietary ingestion has been described in the present study for the first time. The metabolic capacity for isoflavones by domestic cats appears to be efficient, with only minimal proportions of the ingested amount detected in their unconjugated forms. This has implications for the potential of isoflavones to exert physiological activity in the domestic cat when consumed at concentrations representative of typical dietary intake

Writing Class In and Out: Constructions of Class in Elite Businesswomen's Autobiographies

The final version of this paper has been published in Sociology, November 2020 by SAGE Publications Ltd, All rights reserved. © The Authors, 2020. It is available at: https://journals.sagepub.com/home/socThis article explores how meanings of class are constructed in elite businesswomen’s autobiographies. It extends existing sociological studies of elites in two ways. First, by theorising the cultural mechanisms that contribute to the reproduction of business elites, and second, by examining the hitherto under-researched gendered aspects of the reproduction of business elites, and the legitimisation of wealth. We show how these autobiographical texts acknowledge class yet render it irrelevant through discursive repertoires of ordinariness, a universal gender struggle and the unimportance of wealth. We argue that in doing so the genre of elite businesswomen autobiographies contributes to the cultural erasure of class, perpetuating messages that contribute to the creation of a cultural milieu in which class and wealth inequalities remain unquestioned. In an economic context where social disparities continue to grow, the article importantly furthers our understanding of the cultural means by which a plutocratic elite holds on to power

Tendencies of a dominant party system in the Free State Legislature (1994-2008)

Dominant party tendencies exist either when a single party enjoys monopoly of power through the exclusion of other parties, or when the electorate continues to re-elect the same party despite the existence of other political parties. Dominant party systems display various characteristics the tendency to rule for a prolonged period of time; complacency and corruption; competition within the dominant party; a weak and ineffective opposition; and, a blurring of lines between the party and the state. Under the apartheid regime, the National Party dominated the political system. In 1994, through a process of transformation, South Africa held its first democratic election. The African National Congress (ANC) won the election and successive elections, and has since governed by majority. This has led critics to argue that South Africa is becoming a dominant party system. This article discusses dominant party tendencies in the Free State Legislature. In the four elections held since this transformation process of democratisation began, namely 1994, 1999, 2004 and 2009, the ANC dominated the Legislature whilst the opposition remained weak and ineffective, with no viable alternative for the electorate. Despite protests against service delivery and transformation projects, the electorate continued to re-elect the ANC. These tendencies reinforced the pattern of ANC dominance and weak opposition

Loss of endogenous thymosin β4 accelerates glomerular disease

Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin β4 regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin β4 improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin β4 in the kidney is unknown. We demonstrate that thymosin β4 is expressed prominently in podocytes of developing and adult mouse glomeruli. Global loss of thymosin β4 did not affect healthy glomeruli, but accelerated the severity of immune-mediated nephrotoxic nephritis with worse renal function, periglomerular inflammation, and fibrosis. Lack of thymosin β4 in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin β4 in the migration of these cells. Thymosin β4 knockdown in cultured podocytes also increased migration in a wound-healing assay, accompanied by F-actin rearrangement and increased RhoA activity. We propose that endogenous thymosin β4 is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression