Targeted cell imaging properties of a deep red luminescent iridium(III) complex conjugated with a c-Myc signal peptide

A nuclear localisation sequence (NLS) peptide, PAAKRVKLD, derived from the human c-Myc regulator gene, has been functionalised with a long wavelength (λex = 550 nm; λem = 677 nm) cyclometalated organometallic iridium(III) complex to give the conjugate Ir-CMYC. Confocal fluorescence microscopy studies on human fibroblast cells imaged after 18–24 h incubation show that Ir-CMYC concentrations of 80–100 μM promote good cell uptake and nuclear localisation, which was confirmed though co-localisation studies using Hoechst 33342. In comparison, a structurally related, photophysically analogous iridium(III) complex lacking the peptide sequence, Ir-PYR, showed very different biological behaviour, with no evidence of nuclear, lysosomal or autophagic vesicle localisation and significantly increased toxicity to the cells at concentrations >10 μM that induced mitochondrial dysfunction. Supporting UV-visible and circular dichroism spectroscopic studies show that Ir-PYR and Ir-CMYC display similarly low affinities for DNA (ca. 103 M−1), consistent with electrostatic binding. Therefore the translocation and nuclear uptake properties of Ir-CMYC are attributed to the presence of the PAAKRVKLD nuclear localisation sequence in this complex

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

Using standardized fishery data to inform rehabilitation efforts

Lakes and reservoirs progress through an aging process often accelerated by human activities, resulting in degradation or loss of ecosystem services. Resource managers thus attempt to slow or reverse the negative effects of aging using a myriad of rehabilitation strategies. Sustained monitoring programs to assess the efficacy of rehabilitation strategies are often limited; however, long-term standardized fishery surveys may be a valuable data source from which to begin evaluation.We present 3 case studies using standardized fishery survey data to assess rehabilitation efforts stemming from the Nebraska Aquatic Habitat Plan, a large-scale program with the mission to rehabilitate waterbodies within the state. The case studies highlight that biotic responses to rehabilitation efforts can be assessed, to an extent, using standardized fishery data; however, there were specific areas where minor increases in effort would clarify the effectiveness of rehabilitation techniques. Management of lakes and reservoirs can be streamlined by maximizing the utility of such datasets to work smarter, not harder. To facilitate such efforts, we stress collecting both biotic (e.g., fish lengths and weight) and abiotic (e.g., dissolved oxygen, pH, and turbidity) data during standardized fishery surveys and designing rehabilitation actions with an appropriate experimental design

Understanding Sportsperson Retention and Reactivation Through License Purchasing Behavior

Most state and provincial fish and wildlife agencies have access to important information about patterns in sportsperson participation through their license databases. Using transaction data from Nebraska Game and Parks Commission’s electronic hunting and fishing license system, we tracked license purchases of Nebraska, USA, resident license holders in 2010 through 2017. We categorized sportspersons by gender and yearly purchases as hunting only (Hunter), fishing only (Angler), a combination of hunting and fishing (Hunter–Angler), or no purchases (Inactive). The probability of movement among active sportsperson groups was limited and varied little based on initial group participation. The Angler group had the greatest probability of an individual transitioning to the Inactive group (females = 0.39; males = 0.33). The Hunter–Angler group had the greatest probability of an individual remaining within the same group (females = 0.65; males = 0.76). There was a relatively low probability of an individual in the Hunter group moving to the Angler group and vice versa (≤0.02). The sportsperson population is dynamic and understanding patterns of sportsperson participation is important for the future of fish and wildlife management in North America. Using data readily available to most fish and wildlife agencies has the potential to significantly improve our understanding of hunter and angler participation and aid management agencies and conservation organizations in the development of more effective strategies for managing sportspersons

An open-sourced, web-based application to improve our ability to understand hunter and angler purchasing behavior from license data.

State fish and wildlife agencies rely on hunters and anglers (i.e., sportspersons) to fund management actions through revenue generated from license sales and excise taxes on hunting and fishing equipment. There is a need to develop new techniques that bridge the information gap on participation and provide agencies with an understanding of sportspersons at a resolution that can more directly inform efforts to engage sportspersons. Monitoring sportsperson participation using information about their license-purchasing behavior has the potential to reveal important patterns in recruitment (first-time purchase of a hunting or fishing license), retention (continued purchase of licenses across multiple years), and reactivation (purchase a license after several years with no purchases). Providing up-to-date information on what licenses are purchased, when and by whom may prove invaluable to managers and policy makers. We present a customizable, open-source, web-based application-huntfishapp-that allows the user to query and interact with a structured query language (SQL) hunting and fishing license database. The huntfishapp serves as an informational resource and tool that provides a framework to share information on license sales across an agency, with intent of increasing understanding of (a) sportspersons and (b) how management decisions affect sportspersons. Data dashboards, like the huntfishapp, allow agencies and non-governmental organizations to become more knowledgeable of their customer base and provide a greater understanding of management-decision effects on hunting and fishing participation