Pushing the limits of magnetic anisotropy in trigonal bipyramidal Ni(II)

Monometallic complexes based on 3d transition metal ions in certain axial coordination environments can exhibit appreciably enhanced magnetic anisotropy, important for memory applications, due to stabilisation of an unquenched orbital moment. For high-spin trigonal bipyramidal Ni(II), if competing structural distortions can be minimised, this may result in an axial anisotropy that is at least an order of magnitude stronger than found for orbitally non-degenerate octahedral complexes. Broadband, high-field EPR studies of [Ni(MDABCO)2Cl3]ClO4 (1) confirm an unprecedented axial magnetic anisotropy, which pushes the limits of the familiar spin-only description. Crucially, compared to complexes with multidentate ligands that encapsulate the metal ion, we see only a very small degree of axial symmetry breaking. 1 displays field-induced slow magnetic relaxation, which is rare for monometallic Ni(II) complexes due to efficient spin–lattice and quantum tunnelling relaxation pathways

Investigation of the magnetic anisotropy in a series of trigonal bipyramidal Mn(II) complexes

Understanding how the magnetic anisotropy in simple coordination complexes can be manipulated is instrumental to the development of single-molecule magnets (SMMs). Clear strategies can then be designed to control both the axial and transverse contributions to the magnetic anisotropy in such compounds, and allow them to reach their full potential. Here we show a strategy for boosting the magnetic anisotropy in a series of trigonal bipyramidal Mn(II) complexes – [MnCl3(HDABCO)(DABCO)] (1), [MnCl3(MDABCO)2]·[ClO4] (2), and [MnCl3(H2O)(MDABCO)] (3). These have been successfully synthesised using the monodentate [DABCO] and [MDABCO]+ ligands. Through static (DC) magnetic measurements and detailed theoretical investigation using ab initio methods, the magnetic anisotropy of each system has been studied. The calculations reveal that the rhombic zero-field splitting (ZFS) term (E) can be tuned as the symmetry around the Mn(II) ion is changed. Furthermore, an in silico investigation reveals a strategy to increase the axial ZFS parameter (D) of trigonal bipyramidal Mn(II) by an order of magnitude

A large axial magnetic anisotropy in trigonal bipyramidal Fe(II)

The first trigonal bipyramidal Fe(II) complex to display slow relaxation of magnetisation has been isolated, with this behaviour found to arise through a combination of a large magnetic anisotropy (D = -27.5 cm-1) and a pseudo-D3h symmetry at the Fe(II) centre, as investigated through ab initio and magnetic studies

Rudolph the red nosed reindeer had a very bioluminescent nose. A reply to van der Hoven et al. 2012

Research published in Deinsea by van der Hoven et al. (2012) identifies the cause of Rudolph’s infamous red nose to be the consequence of hyperemia of the nasal mucosa induced by the exertion of pulling a heavy load. Van der Hoven et al. (2012) claim that the excessive stresses endured whilst flying with Santa Claus and the sleigh in tow resulted in cerebral and bodily hyperthermia, overworking the nasal cooling system, causing the nose to glow. Whilst we recognise van der Hoven et al.’s (2012) central tenet of highly vascularized nasal mucosa in reindeer (Rangifer tarandus Linnaeus, 1758) helping regulate nasal heat exchange, we concluded that this is unlikely to be the causal factor of Rudolph’s particularly iridescent appendage for multiple reasons

Between empathy and anger: healthcare workers’ perspectives on patient disengagement from antiretroviral treatment in Khayelitsha, South Africa - a qualitative study

Background & objectives The benefits of long-term adherence to antiretroviral treatment (ART) are countered by interruptions in care or disengagement from care. Healthcare workers (HCWs) play an important role in patient engagement and negative or authoritarian attitudes can drive patients to disengage. However, little is known about HCW perspectives on disengagement. We explored HCWs’ perspectives on ART disengagement in Khayelitsha, a peri-urban area in South Africa with a high HIV burden. Method Semi-structured interviews were conducted in English with 30 HCWs in a primary care HIV clinic to explore their perspectives of patients who disengage from ART. Participants included doctors, nurses, counsellors, social workers, data clerks, security guards, and allied health professionals. The interview guide included questions that asked HCWs to give examples of patients who interrupt treatment, their perceptions of people who disengage from care and their feelings when dealing with a patient who is returning to care. All transcripts were audio-recorded, transcribed, and analysed using an inductive thematic analysis approach. Results Most staff were knowledgeable about the complexities of disengagement and highlighted potential barriers to sustaining adherence on ART, including mental health challenges and non-disclosure to family and partners. Participants expressed empathy for patients who interrupted treatment, particularly when discussing potential barriers to continued engagement in care. However, many also expressed feelings of anger and frustration towards these patients, partly because they reported these patients increase workload. Some staff, mainly those taking chronic medication themselves, perceived that patient who disengage from ART do not take adequate responsibility for their health. Conclusion Lifelong engagement with HIV care is influenced by many factors, including HCW interactions. Findings from this study show that staff had contradictory feelings towards disengaged patients, experiencing both empathy and anger. This understanding could contribute to the development of more nuanced interventions to support staff and encourage true person-centred care, to improve patient outcomes

Antigen Localization Influences the Magnitude and Kinetics of Endogenous Adaptive Immune Response to Recombinant Salmonella Vaccines

The use of recombinant attenuated Salmonella vaccine (RASV) strains is a promising strategy for presenting heterologous antigens to the mammalian immune system to induce both cellular and humoral immune responses. However, studies on RASV development differ on where heterologous antigens are expressed and localized within the bacterium, and it is unclear how antigen localization modulates the immune response. Previously, we exploited the plasmid-encoded toxin (Pet) autotransporter system for accumulation of heterologous antigens in cell culture supernatant. In the present study, this Pet system was used to express early secretory antigen 6 (ESAT-6), an immunodominant and diagnostic antigen from Mycobacterium tuberculosis, in Salmonella enterica serovar Typhimurium strain SL3261. Three strains were generated, whereby ESAT-6 was expressed as a cytoplasmic (SL3261/cyto), surface-bound (SL3261/surf), or secreted (SL3261/sec) antigen. Using these RASVs, the relationship between antigen localization and immunogenicity in infected C57BL/6 mice was systematically examined. Using purified antigen and specific tetramers, we showed that mice infected with the SL3261/surf or SL3261/sec strain generated large numbers of Th1 CD4+ ESAT-6+ splenic T cells compared to those of mice infected with SL3261/cyto. While all mice showed ESAT-6-specific antibody responses when infected with SL3261/surf or SL3261/sec, peak total serum IgG antibody titers were reached more rapidly in mice that received SL3261/sec. Thus, how antigen is localized after production within bacteria has a more marked effect on the antibody response than on the CD4+ T cell response, which might influence the chosen strategy to localize recombinant antigen in RASVs

Envisioning a resilient future for biodiversity conservation in the wake of the COVID-19 pandemic

NE/T010401/1 UIDB/04647/2020 UIDP/04647/2020As the COVID-19 pandemic continues to affect societies across the world, the ongoing economic and social disruptions are likely to present fundamental challenges for current and future biodiversity conservation. We review the literature for outcomes of past major societal, political, economic and zoonotic perturbations on biodiversity conservation, and demonstrate the complex implications of perturbation events upon conservation efforts. Building on the review findings, we use six in-depth case studies and the emerging literature to identify positive and negative outcomes of the COVID-19 pandemic, known and anticipated, for biodiversity conservation efforts around the world. A number of similarities exist between the current pandemic and past perturbations, with experiences highlighting that the pandemic-induced declines in conservation revenue and capacity, livelihood and trade disruptions are likely to have long-lasting and negative implications for biodiversity and conservation efforts. Yet, the COVID-19 pandemic also brought about a global pause in human movement that is unique in recent history, and may yet foster long-lasting behavioural and societal changes, presenting opportunities to strengthen and advance conservation efforts in the wake of the pandemic. Enhanced collaborations and partnerships at the local level, cross-sectoral engagement, local investment and leadership will all enhance the resilience of conservation efforts in the face of future perturbations. Other actions aimed at enhancing resilience will require fundamental institutional change and extensive government and public engagement and support if they are to be realised. The pandemic has highlighted the inherent vulnerabilities in the social and economic models upon which many conservation efforts are based. In so doing, it presents an opportunity to reconsider the status quo for conservation, and promotes behaviours and actions that are resilient to future perturbation. A free Plain Language Summary can be found within the Supporting Information of this article.publishersversionpublishe

Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

Cluster of Sylvatic Epidemic Typhus Cases Associated with Flying Squirrels, 2004–2006

Infected persons had slept in an infested cabin

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis