The de‐repression of transposable elements (TEs) in mammalian genomes is thought to contribute to genome instability, inflammation, and ageing, yet is viewed as a cell‐autonomous event. In contrast to mammalian cells, prokaryotes constantly exchange genetic material through TEs, crossing both cell and species barriers, contributing to rapid microbial evolution and diversity in complex communities such as the mammalian gut. Here, it is proposed that TEs released from prokaryotes in the microbiome or from pathogenic infections regularly cross the kingdom barrier to (...) the somatic cells of their eukaryotic hosts. It is proposed this horizontal transfer of TEs from microbe to host is a stochastic, ongoing catalyst of genome destabilization, resulting in structural and epigenetic variations, and activation of well‐evolved host defense mechanisms contributing to inflammation, senescence, and biological ageing. It is proposed that innate immunity pathways defend against the horizontal acquisition of microbial TEs, and that activation of this pathway during horizontal transposon transfer promotes chronic inflammation during ageing. Finally, it is suggested that horizontal acquisition of prokaryotic TEs into mammalian genomes has been masked and subsequently under‐reported due to flaws in current sequencing pipelines, and new strategies to uncover these events are proposed. (shrink)

Antimicrobial resistance (AMR) is one of the defining global health threats of our time, but no international legal instrument currently offers the framework and mechanisms needed to address it. Fortunately, the actions needed to address AMR have considerable overlap with the actions needed to confront other pandemic threats.

Globalization, with its undisputed benefits, also presents complex moral challenges that business leaders cannot ignore. Some of this moral complexity is attributable to the scope and nature of specific issues like climate change, intellectual property rights, economic inequity, and human rights. More difficult aspects of moral complexity are the structure and dynamics of human moral judgment and the amplified universe of global stakeholders with competing value claims and value systems whose interests must be considered and often included in the decision-making (...) process. While managing moral challenges is considered in management literature to be a legitimate and crucial function of business leadership, the complexity of moral challenges in a globalized business culture stretches the managerial capacities of individuals who rely on a personal moral compass and their own wisdom traditions of philosophy or religion for guidance. The Global Moral Compass introduces an expanded epistemic value framework as an aid to understanding and managing moral complexity in a globalized business culture. (shrink)

This author offers of narrative of hope in response to the coronavirus pandemic by viewing it as a wake-up call to lean into the adaptive moral challenge of stewardship for the future of humanity and the planet. Acknowledging the many material and social benefits of a global regime of free market urbanism built on advances in science and technology, this is a point in geohistory, the Anthropocene, when the impact of human activities on the Earth has begun to outcompete natural (...) processes. The coronavirus has illuminated systemic moral failures and new moral challenges of the Anthropocene that call for adaptive response if we are to build a hopeful future for humanity and the planet. Pointing to millennia of human adaptive response to threats and disasters, the author asserts an evolutionary hardiness attributable as much to moral capacities as rational intelligence as a singularly defining trait fueling millennia of human adaptive learning and thrival. The current pandemic is the latest point in humanity’s moral evolution of adaptive response to moments of urgent threat that have tested, expanded, and defined our character and moral capacities as a species. Rather than falter under the moral burden of the coronavirus threat and its consequences, the author views this pivotal point as an opportunity to stretch human moral horizons by taking responsibility for the urgent moral challenges we have created and inventing new ethical frameworks and tools that will lead us to new moral understandings and solutions to the moral challenges we face. (shrink)

Basic proteins and nucleic acids are assembled into complexes in a reaction that must be facilitated by nuclear chaperones in order to prevent protein aggregation and formation of non‐specific nucleoprotein complexes. The nucleophosmin/nucleoplasmin (NPM) family of chaperones [NPM1 (nucleophosmin), NPM2 (nucleoplasmin) and NPM3] have diverse functions in the cell and are ubiquitously represented throughout the animal kingdom. The importance of this family in cellular processes such as chromatin remodeling, genome stability, ribosome biogenesis, DNA duplication and transcriptional regulation has led to (...) the rapid growth of information available on their structure and function. The present review covers different aspects related to the structure, evolution and function of the NPM family. Emphasis is placed on the long‐term evolutionary mechanisms leading to the functional diversification of the family members, their role as chaperones (particularly as it pertains to their ability to aid in the reprogramming of chromatin), and the importance of NPM2 as an essential component of the amphibian chromatin remodeling machinery during fertilization and early embryonic development. BioEssays 29: 49–59, 2007. © 2006 Wiley Periodicals, Inc. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Prior generations’ electoral crises (e.g., gerrymandering) have dealt mainly with political maneuverings around geographical shifts. We analyze four recent (1998–2003) American electoral crises: the Clinton impeachment controversy, the 2000 Florida presidential election, the Texas legislators’ flight to Oklahoma and New Mexico, and the California gubernatorial recall. We show that in each case temporal manipulation was at least as important as geographical. We highlight emergent electoral practices surrounding the manipulation of time, which we dub “temporal gerrymandering.” We suggest a theory of (...) postmodern electoral crises, in which the rules of time and space are simultaneously in flux. These crises expose concerns with early American democratic theory, which was based on an understanding of “the people” as geographically and temporally unidimensional. Representative systems, therefore, were designed largely without reference to geographic and temporal complexity. (shrink)

BackgroundOther Specified Feeding and Eating Disorders are characterized by less frequent symptoms or symptoms that do not meet full criteria for another eating disorder. Despite its high prevalence, limited research has examined differences in severity and treatment outcome among patients with OSFED compared to threshold EDs [Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder ]. The purpose of the current study was to examine differences in clinical presentation and treatment outcome between a heterogenous group of patients with OSFED or threshold (...) EDs.MethodPatients with threshold EDs or OSFED presenting for eating disorder treatment completed self-report questionnaires at intake and discharge to assess eating disorder symptoms, depression symptoms, impairment, and self-esteem.ResultsAt intake, OSFED patients showed lower eating concerns compared to patients with BN, but similar levels compared to AN and BED. The OSFED group showed higher restraint symptoms compared to BED, and similar restraint to AN and BN. Global symptoms as well as shape and weight concerns were similar between OSFED and threshold ED groups. There were no differences between diagnostic groups in self-esteem, depression scores, or symptom change from intake to discharge.DiscussionOur findings suggest that individuals with OSFED showed largely similar ED psychopathology and similar decreases in symptoms across treatment as individuals diagnosed with threshold EDs. Taken together, findings challenge the idea that OSFED is less severe and more resistant to treatment than threshold EDs. (shrink)

Ensuring that life-saving antimicrobials remain available as effective treatment options in the face of rapidly rising levels of antimicrobial resistance will require a massive and coordinated global effort. Setting a collective direction for progress is the first step towards aligning global efforts on AMR. This process would be greatly accelerated by adopting a unifying global target — a well-defined global target that unites all countries and sectors. The proposed pandemic instrument — with its focus on prevention, preparedness and response — (...) represents an ideal opportunity to develop and adopt a unifying global target that catalyzes global action on AMR. We propose three key characteristics of a unifying global target for AMR that — if embedded within the pandemic preparedness instrument — could rally public support, funding, and political commitment commensurate with the scale of the AMR challenge. (shrink)

As Fragment 46 of the first book of Sallust's Histories Maurenbrecher prints: Magnis operibus perfectis obsidium cepit per L. Catilinam legatum. This he takes in effect to mean that Lucretius Ofella after the completion of great siege works received reinforcements brought by L. Catiline legate of Sulla. The interpretation depends largely upon his contention that the phrase obsidium cepit is to be taken as equivalent to subsidium cepit, for which he claims the authority, ultimately, of Verrius Flaccus as represented by (...) Festus p. 193M s.v. obsidium. Though opinions may occasionally have differed as to the precise event documented by the fragment, this central assumption seems to have gone unchallenged by historians. Yet it rests upon remarkably insecure foundations. The reading cepit has scant authority and the interpretation of obsidium as subsidium none at all. It is in fact the result of misunderstanding the passage of Festus in which the text is embedded. In Lindsay's edition the Festus entry which is here quoted in full runs as follows: Obsidium tamquam praesidium, subsidium recte dicitur, cuius etiam auctor C. Laelius pro se apud populum : ‘Ut in nobis terra marique simul obsidium facerent.’ Et Sallustius historiarum I : ‘Magnis operibus perfectis obsidium coepit per L. Catilinam legatum.’ Coepit is the reading of the manuscript F, which has been generally accepted, while cepit appears only in the Aldine edition where it may well be an emendation or even an error, there being no obvious independent source which might have provided it. For Maurenbrecher it was merely the ‘correction’ of Corte who produced the earliest roughly chronological arrangement of the fragments of Sallust's Histories. (shrink)