Championing a move from sustainability to Planetary Health in nursing curriculum.

In this paper, we review the progress on developing sustainability-related content in the Bachelor of Nursing curriculum in Aotearoa New Zealand and engage with Planetary Health. Sustainability in nurse education is explored and the concept of sustainability-practising graduates is promoted. THE ISSUE: We have seen ambivalence towards sustainability persisting amongst nurse educators and students, and sustainability-related content discarded. Despite this, we continue to recognise that sustainability is closely related to climate change which is the greatest threat to planetary, human, and animal health and as such is an essential component of nurse education and practice. Never has there been a timelier reminder of nurses' responsibility to recognise we are ideally placed to contribute to, and help lead, the health response to climate change and champion sustainability. A SYSTEMS-THINKING APPROACH: This response includes a systems-thinking approach to understanding climate change and the impact on health, nursing's responsibility to address climate change, promote health, and respond to health needs. As we revise our current Bachelor of Nursing curriculum, it is timely to review how our sustainability content and thinking has progressed since our previous review in 2017. We are mindful of the need to continue championing this topic, ensuring it is situated at the forefront of nurse education. We propose that a gradual and purposeful shift towards a Planetary Health focus will help to counter the sustainability fatigue and ambivalence we have noted amongst our colleagues and students, ensuring our revised Bachelor of Nursing curriculum is future proofed.

The extracellular vesicle proteomes of Sorghum bicolor and Arabidopsis thaliana are partially conserved.

Plant extracellular vesicles (EVs) are membrane-bound organelles involved mainly in intercellular communications and defense responses against pathogens. Recent studies have demonstrated the presence of proteins, nucleic acids including small RNAs, and lipids along with other metabolites in plant EVs. Here, we describe the isolation and characterization of EVs from sorghum (Sorghum bicolor). Nanoparticle tracking analysis, dynamic light scattering, and cryo-electron tomography showed the presence of a heterogeneous population of EVs isolated from the apoplastic wash of sorghum leaves. Cryo-electron microscopy revealed that EVs had a median size of 110 nm and distinct populations of vesicles with single or multiple lipid bilayers and low or high amounts of contents. The heterogeneity was further supported by data showing that only a subset of EVs that were stained with a membrane dye, Potomac Gold, were also stained with the membrane-permeant esterase-dependent dye, calcein acetoxymethyl ester. Proteomic analysis identified 437 proteins that were enriched in multiple EV isolations, with the majority of these also found in the EV proteome of Arabidopsis (Arabidopsis thaliana). These data suggest a partial conservation of EV contents and function between the monocot, sorghum, and a distantly related eudicot, Arabidopsis.

The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson's Disease.

The accumulation and aggregation of alpha-synuclein (α-Syn) are pathological processes associated with Parkinson's disease, indicating that the regulation of protein is a crucial etiopathological mechanism. Interestingly, human serum and cerebrospinal fluid contain autoantibodies that recognize α-Syn. This potentially demonstrates an already existing, naturally decomposing, and protective system. Thus, quantitative or qualitative alterations, such as the modified antigen binding of so-called naturally occurring autoantibodies against α-Syn (nAbs-α-Syn), may induce disease onset and/or progression. We investigated the serum titers and binding characteristics of nAbs-α-Syn in patients suffering from sporadic Parkinson's disease (n = 38), LRRK2 mutation carriers (n = 25), and healthy controls (n = 22). METHODS: Titers of nAbs-α-Syn were assessed with ELISA and binding affinities and kinetics with SPR. Within the patient cohort, we discriminated between idiopathic and genetic (LRRK2-mutated) variants. RESULTS: ELISA experiments revealed no significant differences in nAbs-α-Syn serum titers among the three cohorts. Moreover, the α-Syn avidity of nAbs-α-Syn was also unchanged. CONCLUSIONS: Our findings indicate that nAbs-α-Syn concentrations or affinities in healthy and diseased persons do not differ, independent of mutations in LRRK2.

Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress.

The most abundant cellular divalent cations, Mg2+ (mM) and Ca2+ (nM-µM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but the physiological significance of this competition remains elusive. In mice consuming a Western diet, genetic ablation of the mitochondrial Mg2+ channel Mrs2 prevents weight gain, enhances mitochondrial activity, decreases fat accumulation in the liver, and causes prominent browning of white adipose. Mrs2 deficiency restrains citrate efflux from the mitochondria, making it unavailable to support de novo lipogenesis. As citrate is an endogenous Mg2+ chelator, this may represent an adaptive response to a perceived deficit of the cation. Transcriptional profiling of liver and white adipose reveals higher expression of genes involved in glycolysis, ß-oxidation, thermogenesis, and HIF-1α-targets, in Mrs2-/- mice that are further enhanced under Western-diet-associated metabolic stress. Thus, lowering mMg2+ promotes metabolism and dampens diet-induced obesity and metabolic syndrome.

Palliative and end of life care in undergraduate medical education: a survey of New Zealand medical schools.

BACKGROUND: In New Zealand, 34% of deaths occur in the hospital setting where junior doctors are at the frontline of patient care. The death rate in New Zealand is expected to double by 2068 due to the aging population, but many studies report that graduates feel unprepared to care for people near the end of life and find this to be one of the most stressful parts of their work. International guidelines recommend that palliative and end of life care should be a mandatory component of undergraduate medical education, yet teaching varies widely and remains optional in many countries. Little is known about how medical students in New Zealand learn about this important area of clinical practice. The purpose of this study was to investigate the organisation, structure and provision of formal teaching, assessment and clinical learning opportunities in palliative and end of life care for undergraduate medical students in New Zealand. METHODS: Quantitative descriptive, cross-sectional survey of module conveners in New Zealand medical schools. RESULTS: Palliative and end of life care is included in undergraduate teaching in all medical schools. However, there are gaps in content, minimal formal assessment and limited contact with specialist palliative care services. Lack of teaching staff and pressure on curriculum time are the main barriers to further curriculum development. CONCLUSIONS: This article reports the findings of the first national survey of formal teaching, assessment and clinical learning opportunities in palliative and end of life care in undergraduate medical education in New Zealand. There has been significant progress towards integrating this content into the curriculum, although further development is needed to address barriers and maximise learning opportunities to ensure graduates are as well prepared as possible.

Complete Genome Sequence of Rhodococcus qingshengii Strain CL-05, Isolated from Concrete.

Here, we report the complete genome sequence of Rhodococcus qingshengii strain CL-05, which was isolated from pavement concrete in Newark, Delaware. The genome consists of a 6.29-Mbp chromosome and one plasmid (123,183 bp), encodes a total of 5,859 predicted proteins, and has a GC content of 62.5%.

Preparing nurses for palliative and end of life care: A survey of New Zealand nursing schools.

BACKGROUND: Nurses play a vital role in the care of people with advanced life-limiting illnesses, so palliative and end of life care is an essential skill nurses need to learn. Despite numerous reports in the international literature about educational developments in this area, there are widespread inconsistencies in undergraduate education, and graduates continue to report feeling unprepared for this part of their work. Little is known about how New Zealand nursing students learn about this important area of clinical practice. OBJECTIVES: To obtain information about teaching content, organisation, delivery, assessment and clinical learning opportunities in palliative and end of life care in undergraduate nurse education in New Zealand. DESIGN: Quantitative descriptive cross sectional study. SETTINGS: Tertiary education institutions that provide the Bachelor of Nursing programme in New Zealand. PARTICIPANTS: Academic leads and course coordinators. METHODS: National online survey. RESULTS: A total of 13/18 (72%) educational institutions completed the survey. All integrate palliative and end of life care in their teaching with an identified coordinator at 12 (92%) institutions. Between 1 and 10 h of formal teaching is provided at 11 (85%) institutions where lectures and tutorials are most comon. Clinical placements with specialist palliative care providers are scarce and limited to senior students as elective placements. Assessment of student learning in palliative and end of life care is carried out at seven (54%) institutions, and formally evaluated at 12 (92%). Lack of teaching time and clinical placements with palliative care providers are barriers to increased learning opportunities in palliative and end of life care. CONCLUSIONS: This article provides comprehensive information about palliative and end of life care teaching in undergraduate nurse education in New Zealand. Teaching on this subject is not a mandatory requirement so there are inconsistencies in the teaching provided between educational institutions, and significant barriers to development. Mandatory competencies need to be introduced to ensure graduates have the knowledge, skills and attitudes required to provide optimal care for people near the end of life.

Interaction of the Joining Region in Junctophilin-2 With the L-Type Ca2+ Channel Is Pivotal for Cardiac Dyad Assembly and Intracellular Ca2+ Dynamics.

RATIONALE: Ca2+-induced Ca2+ release (CICR) in normal hearts requires close approximation of L-type calcium channels (LTCCs) within the transverse tubules (T-tubules) and RyR (ryanodine receptors) within the junctional sarcoplasmic reticulum. CICR is disrupted in cardiac hypertrophy and heart failure, which is associated with loss of T-tubules and disruption of cardiac dyads. In these conditions, LTCCs are redistributed from the T-tubules to disrupt CICR. The molecular mechanism responsible for LTCCs recruitment to and from the T-tubules is not well known. JPH (junctophilin) 2 enables close association between T-tubules and the junctional sarcoplasmic reticulum to ensure efficient CICR. JPH2 has a so-called joining region that is located near domains that interact with T-tubular plasma membrane, where LTCCs are housed. The idea that this joining region directly interacts with LTCCs and contributes to LTCC recruitment to T-tubules is unknown. OBJECTIVE: To determine if the joining region in JPH2 recruits LTCCs to T-tubules through direct molecular interaction in cardiomyocytes to enable efficient CICR. METHODS AND RESULTS: Modified abundance of JPH2 and redistribution of LTCC were studied in left ventricular hypertrophy in vivo and in cultured adult feline and rat ventricular myocytes. Protein-protein interaction studies showed that the joining region in JPH2 interacts with LTCC-α1C subunit and causes LTCCs distribution to the dyads, where they colocalize with RyRs. A JPH2 with induced mutations in the joining region (mutPG1JPH2) caused T-tubule remodeling and dyad loss, showing that an interaction between LTCC and JPH2 is crucial for T-tubule stabilization. mutPG1JPH2 caused asynchronous Ca2+-release with impaired excitation-contraction coupling after ß-adrenergic stimulation. The disturbed Ca2+ regulation in mutPG1JPH2 overexpressing myocytes caused calcium/calmodulin-dependent kinase II activation and altered myocyte bioenergetics. CONCLUSIONS: The interaction between LTCC and the joining region in JPH2 facilitates dyad assembly and maintains normal CICR in cardiomyocytes.

Inhibition of IL-2 or NF-κB Subunit c-Rel-Dependent Signaling Inhibits Expansion of Regulatory T Cells During Acute Friend Retrovirus Infection.

In retroviral infections, different immunological mechanisms are involved in the development of a chronic infection. In the Friend virus (FV) model, regulatory T cells (Tregs) were found to induce CD8+ T cell dysfunction before viral clearance is achieved and thus contribute to viral chronicity. Although studied for decades, the exact suppressive mechanisms of Tregs in the FV model remain elusive and an unavailable therapeutic target. However, extracellular IL-2 and intracellular NF-κB signaling were shown to be important pathways for Treg expansion and activation. Therefore, we decided to focus on these two pathways to test therapeutic approaches inhibiting Treg activation during FV infection. In this study, we show that the inhibition of either IL-2 or the NF-κB subunit c-Rel, impaired Treg expansion and activation at 2 weeks post-FV infection. Total numbers of Tregs as well as activated Tregs were reduced in FV-infected mice after treatment with anti-IL-2 antibodies or the c-Rel blocking reagent pentoxifylline. Surprisingly, this did not affect the expansion or function of virus-specific CD8+ T cells nor viral loads in the spleen. However, our data suggest that neutralization of IL-2 as well as blocking c-Rel efficiently inhibits virus-induced Treg expansion.

Discovery of a bone-like blood particle in the peripheral circulation of humans and rodents.

OBJECTIVE: To characterize ossified bone marrow blood vessels and confirm the presence of ossified particles (OSP) in humans and rodents. METHODS: Human bone marrow blood vessels were processed for scanning and transmission electron microscopy. Whole blood samples were collected from younger (26-39 years; n = 6) and older (55-63 years; n = 6) volunteers and male Fischer-344 rats (1 month, n = 7; 6 months, n = 7; 12 months, n = 7; 18-months, n = 6; 24 months, n = 8). OSP in the whole blood samples were sorted and imaged with microscopy to determine diameter, circularity, and solidity. Additionally, the chemical composition of OSP was determined via elemental analysis. RESULTS: SEM revealed two types of ossified bone marrow blood vessels: that is, "transitioning" and "ossified." OSP were adhered to the surface of transitioning vessels and theoretically gain access to and circulate within the blood. The majority of OSP were ≤15 µm in diameter, but many were of sufficient size to serve as emboli (ie, >15 µm).OSP were predominately oblong in shape and several had jagged tips and edges. CONCLUSIONS: We introduce a novel, bone-like blood particle that may be diagnostic of bone marrow blood vessel ossification. Further, OSP may associate with several disease states (eg, atherosclerosis).

Chronic retroviral infection of mice promotes tumor development, but CD137 agonist therapy restores effective tumor immune surveillance.

T cell responses are crucial for anti-tumor immunity. In chronic viral infections, anti-tumor T cell responses can be compromised due to various immunological mechanisms, including T cell exhaustion. To study mechanisms of anti-tumor immunity during a chronic viral infection, we made use of the well-established Friend virus (FV) mouse model. Chronically FV-infected mice are impaired in their ability to reject FBL-3 cells-a virus-induced tumor cell line of C57BL/6 origin. Here we aimed to explore therapeutic strategies to overcome the influence of T cell exhaustion during chronic viral infection, and reactivate effector CD8+ and CD4+ T cells to eliminate tumor cells. For T cell stimulation, agonistic antibodies against the tumor necrosis factor receptor (TNFR) superfamily members CD137 and CD134 were used, because they were reported to augment the cytotoxic program of T cells. αCD137 agonistic therapy, but not αCD134 agonistic therapy, resulted in FBL-3 tumor elimination in chronically FV-infected mice. CD137 stimulation significantly enhanced the cytotoxic activity of both CD4+ and CD8+ T cells, which were both required for efficient tumor control. Our study suggests that agonistic antibodies to CD137 can efficiently enhance anti-tumor immunity even in the setting of chronic viral infection, which might have promising therapeutic applications.

An undergraduate educational model for developing sustainable nursing practice: A New Zealand perspective.

In this article we reflect on the concept of sustainability and in particular, sustainability within our undergraduate nursing programme. Given the complexity of global environmental change and the prediction that this will impact on health, nurses need to be responsive, knowledgeable and prepared to act on these changes (Anåker and Elf, 2014). Therefore as nurse educators we are responsible for ensuring that undergraduate nursing students are prepared for this reality. Sustainability is a relatively new concept emerging in the discipline of nursing. It is a multifaceted concept embedded within a systems framework, influenced by international, national and local factors. The concept of sustainability can be difficult to articulate and to evidence in daily nursing practice. Student nurses at the School of Nursing, Otago Polytechnic, Dunedin, are expected to meet the graduate profile indicating that they are a sustainability-practicing graduate on completion of their degree programme. As faculty staff, we have been encouraged to explore the concept of sustainability and how it relates to nursing practice. An in-depth review of the international literature, engagement of faculty colleagues, development of frameworks, and mapping of the educational content within the Bachelor of Nursing programme, has led us to develop a model for conveying and teaching sustainable practice.

Characterization of Protein-Excipient Microheterogeneity in Biopharmaceutical Solid-State Formulations by Confocal Fluorescence Microscopy.

Protein-stabilizer microheterogeneity is believed to influence long-term protein stability in solid-state biopharmaceutical formulations and its characterization is therefore essential for the rational design of stable formulations. However, the spatial distribution of the protein and the stabilizer in a solid-state formulation is, in general, difficult to characterize because of the lack of a functional, simple, and reliable characterization technique. We demonstrate the use of confocal fluorescence microscopy with fluorescently labeled monoclonal antibodies (mAbs) and antibody fragments (Fabs) to directly visualize three-dimensional particle morphologies and protein distributions in dried biopharmaceutical formulations, without restrictions on processing conditions or the need for extensive data analysis. While industrially relevant lyophilization procedures of a model IgG1 mAb generally lead to uniform protein-excipient distribution, the method shows that specific spray-drying conditions lead to distinct protein-excipient segregation. Therefore, this method can enable more definitive optimization of formulation conditions than has previously been possible.

Effects of the bacterial algicide IRI-160AA on cellular morphology of harmful dinoflagellates.

The algicide, IRI-160AA, induces mortality in dinoflagellates but not other species of algae, suggesting that a shared characteristic or feature renders this class of phytoplankton vulnerable to the algicide. In contrast to other eukaryotic species, the genome of dinoflagellates is stabilized by high concentrations of divalent cations and transition metals and contains large amounts of DNA with unusual base modifications. These distinctions set dinoflagellates apart from other phytoplankton and suggest that the nucleus may be a dinoflagellate-specific target for IRI-160AA. In this study, morphological and ultrastructural changes in three dinoflagellate species, Prorocentrum minimum, Karlodinium veneficum and Gyrodinium instriatum, were evaluated after short-term exposure to IRI-160AA using super resolution structured illumination microscopy (SR-SIM) and transmission electron microscopy (TEM). Exposure to the algicide resulted in cytoplasmic membrane blebbing, differing chloroplast morphologies, nuclear expansion, and chromosome expulsion and/or destabilization. TEM analysis showed that chromosomes of algicide-treated K. veneficum appeared electron dense with fibrous protrusions. In algicide-treated P. minimum and G. instriatum, chromosome decompaction occurred, while for P. minimum, nuclear expulsion was also observed for several cells. Results of this investigation demonstrate that exposure to the algicide destabilizes dinoflagellate chromosomes, although it was not clear if the nucleus was the primary target of the algicide or if the observed effects on chromosomal structure were due to downstream impacts. In all cases, changes in cellular morphology and ultrastructure were observed within two hours, suggesting that the algicide may be an effective and rapid approach to mitigate dinoflagellate blooms.

Structural defects in cilia of the choroid plexus, subfornical organ and ventricular ependyma are associated with ventriculomegaly.

BACKGROUND: Hydrocephalus is a heterogeneous disorder with multiple etiologies that are not yet fully understood. Animal models have implicated dysfunctional cilia of the ependyma and choroid plexus in the development of the disorder. In this report, we sought to determine the origin of the ventriculomegaly in four Bardet Biedl syndrome (BBS) mutant mouse strains as models of a ciliopathy. METHODS: Evans Blue dye was injected into the lateral ventricle of wild- type and BBS mutant mice to determine whether obstruction of intra- or extra-ventricular CSF flow contributed to ventriculomegaly. Transmission electron microscopy (TEM) was used to examine the ultrastructure of the choroid plexus, subfornical organ (SFO), subcommisural organ (SCO), and ventricular ependyma to evaluate their ultrastructure and the morphology of their primary and motile cilia. RESULTS AND DISCUSSION: No obstruction of intra- or extra-ventricular CSF flow was observed, implying a communicating form of hydrocephalus in BBS mutant mice. TEM analyses of the mutants showed no evidence of choroidal papillomas or breakdown of the blood:CSF barrier. In contrast, structural defects were observed in a subpopulation of cilia lining the choroid plexus, SFO, and ventricular ependyma. These included disruptions of the microtubular structure of the axoneme and the presence of electron-dense vesicular-like material along the ciliary shaft and at the tips of cilia. CONCLUSIONS: Abnormalities in cilia structure and function have the potential to influence ciliary intraflagellar transport (IFT), cilia maintenance, protein trafficking, and regulation of CSF production. Ciliary structural defects are the only consistent pathological features associated with CSF-related structures in BBS mutant mice. These defects are observed from an early age, and may contribute to the underlying pathophysiology of ventriculomegaly.

Gene expression analysis of photoreceptor cell loss in bbs4-knockout mice reveals an early stress gene response and photoreceptor cell damage.

PURPOSE: To identify and characterize gene expression changes associated with photoreceptor cell loss in a Bbs4-knockout mouse model of retinal degeneration. METHODS: Differential gene expression in the eyes of 5-month-old Bbs4(-/-) mice undergoing retinal degeneration were analyzed using gene microarrays (Affymetrix, Santa Clara, CA). Elevated ocular transcripts were confirmed by Northern blotting of RNA from Bbs4(-/-) and three additional mouse models of Bardet-Biedl Syndrome (BBS). TUNEL assays and transmission electron microscopy were used to study cell death and photoreceptor morphology in these mice. RESULTS: Three hundred fifty-four probes were differentially expressed in Bbs4(-/-) eyes compared with controls using a twofold cutoff. Numerous vision-related transcripts decreased because of photoreceptor cell loss. Increased expression of the stress response genes Edn2, Lcn2, Serpina3n, and Socs3 was noted at 5 months of age and as early as postnatal week 4 in the eyes of four BBS mouse model strains. A burst of apoptotic activity in the photoreceptor outer nuclear layer at postnatal week 2 and highly disorganized outer segments by postnatal weeks 4 to 6 was observed in all four strains. CONCLUSIONS: The specific loss of photoreceptors in Bbs4(-)(/)(-) mice allows us to identify a set of genes that are preferentially expressed in photoreceptors compared with other cell types found in the eye and is a valuable resource in the continuing search for genes involved in retinal disease. The molecular and morphologic changes observed in young BBS animal model eyes implies that BBS proteins play a critical, early role in establishing the correct structure and function of photoreceptors.

Formation of microcrystals, micropuddles, and other spatial inhomogenieties in surface reactions under ambient conditions: an atomic force microscopy study of water and nitric acid adsorption on MgO(100) and CaCO3(104).

In this study, atomic force microscopy (AFM) is used to image freshly cleaved MgO(100) and CaCO3(104) as these surfaces undergo reaction with water and nitric acid under ambient conditions of temperature, pressure, and relative humidity. The reaction of water and nitric acid results in the formation of hydroxylated and nitrated surfaces, respectively. It is clear from the AFM images that there are spatial inhomogenieties and surface features that form on micrometer and nanometer length scales as these reactions proceed. These features, which include hillocks, patches, microcrystallites, and micropuddles, are due to surface and phase segregation as a result of facile ion mobility in the presence of adsorbed water. In addition, instabilities and oscillations in the AFM images provide an indication of liquid formation and the deliquescence (i.e., a solid to liquid-phase transition) of nitrate salts as a function of relative humidity.