Nursing in deathworlds: Necropolitics of the life, dying and death of an unhoused person in the United States healthcare industrial complex.

This paper begins with the lived accounts of emergency and critical care medical interventions in which an unhoused person is brought to the emergency department in cardiac arrest. The case is a dramatised representation of the extent to which biopolitical forces via reduction to bare life through biopolitical and necropolitical operations are prominent influences in nursing and medical care. This paper draws on the scholarship of Michel Foucault, Giorgio Agamben, and Achille Mbembe to offer a theoretical analysis of the power dynamics that influence the health care and death care of patients who are caught in the auspices of a neoliberal capitalist healthcare apparatus. This paper offers analysis of the overt displays of biopower over those individuals cast aside as generally unworthy of access to healthcare in a postcolonial capitalist system, in addition to the ways in which humans are reduced to 'bare life' in their dying days. We analyse this case study through Agamben's description of thanatopolitics, a 'regime of death', and the technologies that accompany the dying process, particularly in that of the homo sacer. Additionally, this paper illustrates the ways in which necropolitics and biopower are integral to understanding how the most advanced and expensive medical interventions make visible the political values of the healthcare system and how nurses and healthcare functions in these deathworlds. The purpose of this paper is to develop a greater understanding of biopolitical and necropolitical operations in acute and critical care environments, and to offer guidance to nurses in these spaces as they work to uphold ethical duties in a system that increasingly dehumanises.

The First Evidence of Gibberellic Acid's Ability to Modulate Target Species' Sensitivity to Honeysuckle (Lonicera maackii) Allelochemicals.

Invasive species employ competitive strategies such as releasing allelopathic chemicals into the environment that negatively impact native species. Decomposing Amur honeysuckle (Lonicera maackii) leaves leach various allelopathic phenolics into the soil, decreasing the vigor of several native species. Notable differences in the net negative impacts of L. maackii metabolites on target species were argued to depend on soil properties, the microbiome, the proximity to the allelochemical source, the allelochemical concentration, or environmental conditions. This study is the first to address the role of target species' metabolic properties in determining their net sensitivity to allelopathic inhibition by L. maackii. Gibberellic acid (GA3) is a critical regulator of seed germination and early development. We hypothesized that GA3 levels might affect the target sensitivity to allelopathic inhibitors and evaluated differences in the response of a standard (control, Rbr), a GA3-overproducing (ein), and a GA3-deficient (ros) Brassica rapa variety to L. maackii allelochemicals. Our results demonstrate that high GA3 concentrations substantially alleviate the inhibitory effects of L. maackii allelochemicals. A better understanding of the importance of target species' metabolic properties in their responses to allelochemicals will contribute to developing novel invasive species control and biodiversity conservation protocols and may contribute to applications in agriculture.

Acetylated α-tubulin K394 regulates microtubule stability to shape the growth of axon terminals.

Microtubules are essential to neuron shape and function. Acetylation of tubulin has the potential to directly tune the behavior and function of microtubules in cells. Although proteomic studies have identified several acetylation sites in α-tubulin, the effects of acetylation at these sites remains largely unknown. This includes the highly conserved residue lysine 394 (K394), which is located at the αß-tubulin dimer interface. Using a fly model, we show that α-tubulin K394 is acetylated in the nervous system and is an essential residue. We found that an acetylation-blocking mutation in endogenous α-tubulin, K394R, perturbs the synaptic morphogenesis of motoneurons and reduces microtubule stability. Intriguingly, the K394R mutation has opposite effects on the growth of two functionally and morphologically distinct motoneurons, revealing neuron-type-specific responses when microtubule stability is altered. Eliminating the deacetylase HDAC6 increases K394 acetylation, and the over-expression of HDAC6 reduces microtubule stability similar to the K394R mutant. Thus, our findings implicate α-tubulin K394 and its acetylation in the regulation of microtubule stability and suggest that HDAC6 regulates K394 acetylation during synaptic morphogenesis.

Systematic Evaluation of Protein-Based Nanoparticles for Stable Delivery of Small Interfering RNA.

Developing a delivery vehicle to protect siRNA from degradation is a significant challenge. To solve this challenge, researchers attempted to use protein-based nanoparticles to deliver siRNA with limited to moderate success. However, a systematic investigation of comparing the ability of different protein-based nanoparticles as vehicles to deliver siRNA stably within cells is still unavailable. Therefore, in this study we synthesized a library of both non-targeted (proteinsiRNA) nanoparticles (NPs) and targeted (antibody conjugated protein-siRNA) NPs and evaluated ability to stably deliver siRNA in to cells to silence the gene of interest. We investigated nanoparticles of casein, bovine serum albumin, and gelatin for the delivery of siRNA. We synthesized and characterized a total of 12 nanoconjugates; in these conjugates, we either encapsulated, electrostatically attached, or covalently conjugated siRNA. We evaluated the efficiency of attaching siRNA to nanoconjugates, stability, and cellular delivery. The ability of siRNA to silence the protein of interest in cancer cells was also investigated. Among non-targeted conjugates, BSA matrix imparted relatively high stability to siRNA when encapsulated. Among targeted nanoconjugates, gelatin nanoparticles rendered high stability to siRNA upon covalent conjugation to the surface. On comparing with both targeted and non-targeted NPs for release of siRNA within cells, antibody-gelatin-siRNA conjugate exhibited high release and functional activity (down-regulation of target protein levels) within the cells as confirmed by both fluorescence imaging and Western blotting. In summary, our investigations show that targeted gelatin nanoparticles and non-targeted BSA nanoparticles possess high stability and excellent gene suppression capabilities and warrants further studies. We can extend the results from this study to develop stable siRNA delivery vehicles to specifically silence the protein of interest.

Incorporating social dimensions in planning, managing and evaluating environmental projects.

Most conservation research aims to inform management of environmental challenges, but scientific evidence is used inconsistently in environmental programmes and practice. We used semi-structured retrospective interviews to ask 12 environmental scientists and 14 practitioners (land managers, park rangers, project managers and planners from natural resource management agencies) about factors that facilitated and hindered the use of scientific input during 15 environmental projects. We used the common factors from interviews to develop a process model describing how scientific input informs programmes and practice. The model emphasised the social dimensions of environmental projects which are often overlooked when these projects are planned, managed and evaluated. It highlighted the pivotal role of relationships in achieving outcomes which include creating practical, useful products and tools, and robust, credible and trusted evidence. By clarifying the process of how scientific knowledge informs environmental programmes and practice, the model enabled us to provide guidance about how to undertake transdisciplinary work and suggest indicators to track progress. Although derived from environmental projects, the guidance is likely to apply to other fields, particularly where different disciplines work together.

Microtubule Acetylation Is Required for Mechanosensation in Drosophila.

At the cellular level, α-tubulin acetylation alters the structure of microtubules to render them mechanically resistant to compressive forces. How this biochemical property of microtubule acetylation relates to mechanosensation remains unknown, although prior studies have shown that microtubule acetylation influences touch perception. Here, we identify the major Drosophila α-tubulin acetylase (dTAT) and show that it plays key roles in several forms of mechanosensation. dTAT is highly expressed in the larval peripheral nervous system (PNS), but it is largely dispensable for neuronal morphogenesis. Mutation of the acetylase gene or the K40 acetylation site in α-tubulin impairs mechanical sensitivity in sensory neurons and behavioral responses to gentle touch, harsh touch, gravity, and vibration stimuli, but not noxious thermal stimulus. Finally, we show that dTAT is required for mechanically induced activation of NOMPC, a microtubule-associated transient receptor potential channel, and functions to maintain integrity of the microtubule cytoskeleton in response to mechanical stimulation.

Factors associated with child protection recurrence in Australia.

The aim of the current research was to advance understanding of child protection in Australia by examining the factors associated with recurrence of child protection notifications to the formal child protection system. Extant research has been primarily undertaken in the USA and it is important to understand whether similar factors associated with recurrence actually hold in the Australian context. Administrative data were obtained for a sample of 9608 children first subject to a screened-in report in 2011-12. Children were followed for 12 months. Cox Proportional Hazard models were used to measure associations between 26 independent variables and four types of recurrence: subsequent reports, subsequent investigations, subsequent substantiations, and subsequent intervention. Factors associated with recurrence in Australia were broadly similar to those identified in other jurisdictions, including reports and substantiation for neglect, younger age, prior child protection involvement in the household, and parental characteristics including drug use, mental health problems, and history of maltreatment as a child. As in previous studies, post-investigative service provision was positively associated with recurrence. In prior US research, race did not predict recurrence. However, in the present study, Indigenous Australian children were significantly more likely to be subject to all types of recurrence measured. Future research on recurrence should aim to disentangle the complex relationships between child protection recurrence, child maltreatment, and service delivery. Recurrence is not a good proxy indicator of child safety. The findings have implications for the equity of recurrence-based risk assessment tools as they are applied to indigenous populations.

Effects of mutating α-tubulin lysine 40 on sensory dendrite development.

Microtubules are essential for neuronal structure and function. Axonal and dendritic microtubules are enriched in post-translational modifications that impact microtubule dynamics, transport and microtubule-associated proteins. Acetylation of α-tubulin lysine 40 (K40) is a prominent and conserved modification of neuronal microtubules. However, the cellular role of microtubule acetylation remains controversial. To resolve how microtubule acetylation might affect neuronal morphogenesis, we mutated endogenous α-tubulin in vivo using a new Drosophila strain that facilitates the rapid knock-in of designer αTub84B alleles (the predominant α-tubulin-encoding gene in flies). Leveraging our new strain, we found that microtubule acetylation, as well as polyglutamylation and (de)tyrosination, is not essential for survival. However, we found that dendrite branch refinement in sensory neurons relies on α-tubulin K40. Mutagenesis of K40 reveals moderate yet significant changes in dendritic lysosome transport, microtubule polymerization and Futsch protein distribution in dendrites but not in axons. Our studies point to an unappreciated role for α-tubulin K40 and acetylation in dendrite morphogenesis. While our results are consistent with the idea that acetylation tunes microtubule function within neurons, they also suggest there may be an acetylation-independent requirement for α-tubulin K40.This article has an associated First Person interview with the first author of the paper.

Development of SNP Genotyping Assays for Seed Composition Traits in Soybean.

Seed composition is one of the most important determinants of the economic values in soybean. The quality and quantity of different seed components, such as oil, protein, and carbohydrates, are crucial ingredients in food, feed, and numerous industrial products. Soybean researchers have successfully developed and utilized a diverse set of molecular markers for seed trait improvement in soybean breeding programs. It is imperative to design and develop molecular assays that are accurate, robust, high-throughput, cost-effective, and available on a common genotyping platform. In the present study, we developed and validated KASP (Kompetitive allele-specific polymerase chain reaction) genotyping assays based on previously known functional mutant alleles for the seed composition traits, including fatty acids, oligosaccharides, trypsin inhibitor, and lipoxygenase. These assays were validated on mutant sources as well as mapping populations and precisely distinguish the homozygotes and heterozygotes of the mutant genes. With the obvious advantages, newly developed KASP assays in this study can substitute the genotyping assays that were previously developed for marker-assisted selection (MAS). The functional gene-based assay resource developed using common genotyping platform will be helpful to accelerate efforts to improve soybean seed composition traits.

The complexity of child protection recurrence: The case for a systems approach.

OBJECTIVE: Research on child protection recurrence has found consistent child, family, and case characteristics associated with repeated involvement with the child protection system. Despite the considerable body of empirical research, knowledge about why recurrence occurs, and what can be done to reduce it, is limited. METHOD: This paper reviews the empirical literature and analyses the approaches of prior recurrence research. Four related conceptual challenges are identified: (1) a tendency to conflate child protection recurrence with repeated child maltreatment; (2) uncertainty about how best to operationalize and measure child protection recurrence in research; (3) inconsistency between prevailing explanations for the most frequently observed patterns of recurrence; and (4) difficulty in developing coherent strategies to address child protection recurrence based on research. RESULTS: Addressing these challenges requires a greater consideration of the effects of decision-making in the child protection system on recurrence. This paper proposes a methodology based in systems theory and drawing on existing administrative data to examine the characteristics of the child protection system that may also produce recurrence.

Ludwig's angina: need for including airways and larynx in ultrasound evaluation.

Ludwig's angina is a deep neck space infection. Unlike other abscesses elsewhere in the body, rapid progression of the disease results in serious complications such as airway oedema, distortion, total obstruction with loss of airway and death. Thus, early diagnosis and skilful airway management is necessary. For safe airway management, fibreoptic intubation or tracheostomy under local anaesthesia is recommended.1 We describe a case report where an initial attempt at fibreoptic intubation failed and subsequently bleeding ensued causing difficulty in viewing the larynx by fibreoptic bronchoscopy. Radiological investigations such as ultrasound and computer tomography (CT) are commonly ordered by surgeons and emergency physicians to know the extension of disease, but airways and larynx are seldom included. We discuss the role of ultrasound in airway assessment in such critical cases to ensure safe and uncomplicated airway access.

A CRISPR view of development.

The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system is poised to transform developmental biology by providing a simple, efficient method to precisely manipulate the genome of virtually any developing organism. This RNA-guided nuclease (RGN)-based approach already has been effectively used to induce targeted mutations in multiple genes simultaneously, create conditional alleles, and generate endogenously tagged proteins. Illustrating the adaptability of RGNs, the genomes of >20 different plant and animal species as well as multiple cell lines and primary cells have been successfully modified. Here we review the current and potential uses of RGNs to investigate genome function during development.

Growth control in colon epithelial cells: gadolinium enhances calcium-mediated growth regulation.

Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1-5 µM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet.

A novel split kinesin assay identifies motor proteins that interact with distinct vesicle populations.

Identifying the kinesin motors that interact with different vesicle populations is a longstanding and challenging problem with implications for many aspects of cell biology. Here we introduce a new live-cell assay to assess kinesin-vesicle interactions and use it to identify kinesins that bind to vesicles undergoing dendrite-selective transport in cultured hippocampal neurons. We prepared a library of "split kinesins," comprising an axon-selective kinesin motor domain and a series of kinesin tail domains that can attach to their native vesicles; when the split kinesins were assembled by chemical dimerization, bound vesicles were misdirected into the axon. This method provided highly specific results, showing that three Kinesin-3 family members-KIF1A, KIF13A, and KIF13B-interacted with dendritic vesicle populations. This experimental paradigm allows a systematic approach to evaluate motor-vesicle interactions in living cells.

Neurostimulation for primary headache disorders, part 1: pathophysiology and anatomy, history of neuromodulation in headache treatment, and review of peripheral neuromodulation in primary headaches.

Neurostimulation for primary headaches is being increasingly utilized as a treatment modality. Use of neuromoduation has generated multiple case reports as well as some controlled studies. This article is the first of 2 systematic reviews of available data regarding neurostimulation for primary headache conditions. The pathophysiology, relative anatomy, theoretical mechanisms, and history of neurostimulation for primary headache are covered in this section, Part 1 of 2. The literature regarding peripheral neurostimulatory targets is also reviewed in Part 1. These peripheral targets include: percutaneous nerves, transcranial holocephalic, occipital nerves, auriculotemporal nerves, supraorbital nerves, cervical epidural, and sphenopalatine ganglia. Part 2 will focus on central stimulation, covering vagus nerve, and deep brain stimulation. Part 2 also contains an overall analysis of efficacy, safety, cost, patient selection, and suggestions for further study based on available evidence.

Neurostimulation for primary headache disorders: Part 2, review of central neurostimulators for primary headache, overall therapeutic efficacy, safety, cost, patient selection, and future research in headache neuromodulation.

This article is the second of 2 articles reviewing neurostimulation for primary headaches. In Part 1, we described methods, pathophysiology and anatomy, and history of neuromodulation in the treatment of headache, as well as reviewing the literature on peripheral neuromodulation for primary headaches. Peripheral targets for stimulation include percutaneous nerves, transcranial holocephalic, occipital nerves, auriculotemporal nerves, supraorbital nerves, cervical epidural, and sphenopalatine ganglia. In Part 2, we describe available literature on central neuromodulation in primary headaches. Central stimulation targets include vagus nerve and deep brain structures. Part 2 also analyzes overall therapeutic efficacy, safety, cost, patient selection, and recommendations for further research of neurostimulation modalities based on available data.

fMRI evidence that precision ophthalmic tints reduce cortical hyperactivation in migraine.

BACKGROUND: Certain patterns can induce perceptual illusions/distortions and visual discomfort in most people, headaches in patients with migraine, and seizures in patients with photosensitive epilepsy. Visual stimuli are common triggers for migraine attacks, possibly because of a hyperexcitability of the visual cortex shown in patients with migraine. Precision ophthalmic tints (POTs) are claimed to reduce perceptual distortions and visual discomfort and to prevent migraine headaches in some patients. We report an fMRI visual cortical activation study designed to investigate neurological mechanisms for the beneficial effects of POTs in migraine. METHODS: Eleven migraineurs and 11 age- and sex-matched non-headache controls participated in the study using non-stressful and stressful striped patterns viewed through gray, POT, and control coloured lenses. RESULTS: For all lenses, controls and migraineurs did not differ in their response to the non-stressful patterns. When the migraineurs wore gray lenses or control coloured lenses, the stressful pattern resulted in activation that was greater than in the controls. There was also an absence of the characteristic low-pass spatial frequency (SF) tuning in extrastriate visual areas. When POTs were worn, however, both cortical activation and SF tuning were normalized. Both when observing the stressful pattern and under more typical viewing conditions, the POTs reduced visual discomfort more than either of the other two lenses. CONCLUSION: The normalization of cortical activation and SF tuning in the migraineurs by POTs suggests a neurological basis for the therapeutic effect of these lenses in reducing visual cortical hyperactivation in migraine.

Automated kymograph analysis for profiling axonal transport of secretory granules.

This paper describes an automated method to profile the velocity patterns of small organelles (BDNF granules) being transported along a selected section of axon of a cultured neuron imaged by time-lapse fluorescence microscopy. Instead of directly detecting the granules as in conventional tracking, the proposed method starts by generating a two-dimensional spatio-temporal map (kymograph) of the granule traffic along an axon segment. Temporal sharpening during the kymograph creation helps to highlight granule movements while suppressing clutter due to stationary granules. A voting algorithm defined over orientation distribution functions is used to refine the locations and velocities of the granules. The refined kymograph is analyzed using an algorithm inspired from the minimum set cover framework to generate multiple motion trajectories of granule transport paths. The proposed method is computationally efficient, robust to significant levels of noise and clutter, and can be used to capture and quantify trends in transport patterns quickly and accurately. When evaluated on a collection of image sequences, the proposed method was found to detect granule movement events with 94% recall rate and 82% precision compared to a time-consuming manual analysis. Further, we present a study to evaluate the efficacy of velocity profiling by analyzing the impact of oxidative stress on granule transport in which the fully automated analysis correctly reproduced the biological conclusion generated by manual analysis.

A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration.

A mouse neurological mutant, lister, was identified through a genome-wide N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Homozygous lister mice exhibit profound early-onset and progressive neurological and motor dysfunction. lister encodes a RING finger protein, LISTERIN, which functions as an E3 ubiquitin ligase in vitro. Although lister is widely expressed in all tissues, motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Pathological signs include gliosis, dystrophic neurites, vacuolated mitochondria, and accumulation of soluble hyperphosphorylated tau. Analysis with a different lister allele generated through targeted gene trap insertion reveals LISTERIN is required for embryonic development and confirms that direct perturbation of a LISTERIN-regulated process causes neurodegeneration. The lister mouse uncovers a pathway involved in neurodegeneration and may serves as a model for understanding the molecular mechanisms underlying human neurodegenerative disorders.