Dilution in New Zealand: The Effects of the Tarnishment Limb of Dilution on Free Speech

Calls have been made to introduce trade mark dilution into New Zealand 's trade mark legislation. Currently trade mark protection is limited to the same or similar goods or services to those over which the trade mark is registered, and within this class only certain uses of that trade mark are protected. The positive associations the selling power of famous trade marks is such that their use on dissimilar goods or services can make those goods or services more attractive to consumers. Trade mark dilution recognises that such unauthorised use will weaken the famous trade mark's selling power and proscribes such use. Trade mark dilution, however, goes further and removes the distinction currently made between different uses of a trade mark. Infringement occurs if unauthorised use of the trade mark damages the positive associations the trade mark invokes. Unless exceptions are made to the latter aspect of trade mark dilution, the impact of trade mark dilution upon free speech will be significant

A Multi-Program Assessment of Visiting Pediatric Electives as a Recruitment Tool for Diversity

Certain minority populations are underrepresented in medicine (URM). The visiting clerkship represents a collaborative effort between Undergraduate and Graduate Medical Education that has been reported to help increase URM applicants and residents. Visiting URM student electives in pediatrics at five institutions were examined in an effort to better understand best practices. Financial assistance and mentorship were universal among programs. Most programs reported an increase in URM applicants but variable numbers of matched URM residents

Context-dependent changes in maritime traffic activity during the first year of the COVID-19 pandemic

This article is a contribution of the COVID-19 Bio-Logging Initiative, which is funded in part by the Gordon and Betty Moore Foundation (GBMF9881) and the National Geographic Society (NGS-82515R-20) (both grants to C.R.), and endorsed by the United Nations Decade of Ocean Science for Sustainable Development. Specifically, A.L.’s, R.P.’s and B.R.’s postdoctoral positions were funded by the Gordon and Betty Moore Foundation (GBMF9881), and J.S.’s contributions were funded by the National Geographic Society (NGS-82515R-20). D.W.S. was supported by a Marine Biological Association Senior Research Fellowship with additional support from the Natural Environment Research Council (Discovery Science NE/R00997/X/1) and the European Research Council (Advanced Grant 883583 OCEAN DEOXYFISH).Rapid implementation of human mobility restrictions during the COVID-19 pandemic dramatically reduced maritime activity in early 2020. But where and when activity rebounded, or remained low, during the full extent of 2020 restrictions remains unclear. Using global high-resolution datasets, we reveal a surprising degree of complexity in maritime activity patterns during 2020, yielding a more nuanced picture of how restrictions affected activity. Overall, shipping activity in Exclusive Economic Zones decreased (1.35 %), as expected, however high-seas activity increased (0.28 %). While these annual changes appear modest, there were striking spatially and temporally asynchronous variations in different vessel types’ activity in the second half of 2020, ranging from an > 80 % sustained reduction in passenger vessel activity to a 150 % increase in fishing activity. Results suggest systems-level responses were highly context-dependent, pinpointing areas that experienced significant reductions and spikes in activity, and providing hitherto missing details of COVID-19 impacts on economic and environmental sustainability.Publisher PDFPeer reviewe

Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells

The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential in vivo. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection in vivo

Pathogenic Influenza Viruses and Coronaviruses Utilize Similar and Contrasting Approaches To Control Interferon-Stimulated Gene Responses

ABSTRACT The broad range and diversity of interferon-stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis of the global ISG response and subsequent viral antagonism has yet to be examined. Employing models of the human airway, transcriptomics and proteomics datasets were used to compare ISG response patterns following highly pathogenic H5N1 avian influenza (HPAI) A virus, 2009 pandemic H1N1, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV) infection. The results illustrated distinct approaches utilized by each virus to antagonize the global ISG response. In addition, the data revealed that highly virulent HPAI virus and MERS-CoV induce repressive histone modifications, which downregulate expression of ISG subsets. Notably, influenza A virus NS1 appears to play a central role in this histone-mediated downregulation in highly pathogenic influenza strains. Together, the work demonstrates the existence of unique and common viral strategies for controlling the global ISG response and provides a novel avenue for viral antagonism via altered histone modifications.IMPORTANCEThis work combines systems biology and experimental validation to identify and confirm strategies used by viruses to control the immune response. Using a novel screening approach, specific comparison between highly pathogenic influenza viruses and coronaviruses revealed similarities and differences in strategies to control the interferon and innate immune response. These findings were subsequently confirmed and explored, revealing both a common pathway of antagonism via type I interferon (IFN) delay as well as a novel avenue for control by altered histone modification. Together, the data highlight how comparative systems biology analysis can be combined with experimental validation to derive novel insights into viral pathogenesis

What a girl’s gotta do: the labour of the biopolitical celebrity in austerity Britain

This article debunks the wide-spread view that young female celebrities, especially those who rise to fame through reality shows and other forms of media-orchestrated self-exposure, dodge ‘real’ work out of laziness, fatalism and a misguided sense of entitlement. Instead, we argue that becoming a celebrity in a neoliberal economy such as that of the United Kingdom, where austerity measures disproportionately disadvantage the young, women and the poor is not as irregular or exceptional a choice as previously thought, especially since the precariousness of celebrity earning power adheres to the current demands of the neoliberal economy on its workforce. What is more, becoming a celebrity involves different forms of labour that are best described as biopolitical, since such labour fully involves and consumes the human body and its capacities as a living organism. Weight gain and weight loss, pregnancy, physical transformation through plastic surgery, physical symptoms of emotional distress and even illness and death are all photographically documented and supplemented by extended textual commentary, usually with direct input from the celebrity, reinforcing and expanding on the visual content. As well as casting celebrity work as labour, we also maintain that the workings of celebrity should always be examined in the context of wider cultural and real economies

An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice

Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N4-hydroxycytidine-5′-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses

Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid

Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain