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Palliative care has a very important role in the care of patients with motor neurone disease and their families. There is increasing emphasis on the multidisciplinary assessment and support of patients within guidelines, supported by research. This includes the telling of the diagnosis, the assessment and management of symptoms, consideration of interventions, such as gastrostomy and ventilatory support, and care at the end of life. The aim of palliative care is to enable patients, and their families, to maintain as good a quality of life as possible and helping to ensure a peaceful death.

Reactive oxygen species (ROS), such as${\\rm O}_{2}{}^{-}$and H2O2, play a key role in plant metabolism, cellular signaling, and defense. In leaf cells, the chloroplast is considered to be a focal point of ROS metabolism. It is a major producer of${\\rm O}_{2}{}^{-}$and H2O2during photosynthesis, and it contains a large array of ROS-scavenging mechanisms that have been extensively studied. By contrast, the function of the cytosolic ROS-scavenging mechanisms of leaf cells is largely unknown. In this study, we demonstrate that in the absence of the cytosolic${\\rm H}_{2}{\\rm O}_{2}\\text{-scavenging}$enzyme ascorbate peroxidase 1 (APX1), the entire chloroplastic${\\rm H}_{2}{\\rm O}_{2}\\text{-scavenging}$system of Arabidopsis thaliana collapses, H2O2levels increase, and protein oxidation occurs. We further identify specific proteins oxidized in APX1-deficient plants and characterize the signaling events that ensue in knockout-Apx1 plants in response to a moderate level of light stress. Using a dominant-negative approach, we demonstrate that heat shock transcription factors play a central role in the early sensing of H2O2stress in plants. Using knockout plants for the NADPH oxidase D protein (knockout-RbohD), we demonstrate that RbohD might be required for ROS signal amplification during light stress. Our study points to a key role for the cytosol in protecting the chloroplast during light stress and provides evidence for cross-compartment protection of thylakoid and stromal/mitochondrial APXs by cytosolic APX1.

The autoimmune disease lupus erythematosus (lupus) is characterized by photosensitivity, where even ambient ultraviolet radiation (UVR) exposure can lead to development of inflammatory skin lesions. We have previously shown that Langerhans cells (LCs) limit keratinocyte apoptosis and photosensitivity via a disintegrin and metalloprotease 17 (ADAM17)-mediated release of epidermal growth factor receptor (EGFR) ligands and that LC ADAM17 sheddase activity is reduced in lupus. Here, we sought to understand how the lupus skin environment contributes to LC ADAM17 dysfunction and, in the process, differentiate between effects on LC ADAM17 sheddase function, LC ADAM17 expression, and LC numbers. We show through transcriptomic analysis a shared IFN-rich environment in non-lesional skin across human lupus and three murine models: MRL/lpr, B6.Sle1yaa, and imiquimod (IMQ) mice. IFN-I inhibits LC ADAM17 sheddase activity in murine and human LCs, and IFNAR blockade in lupus model mice restores LC ADAM17 sheddase activity, all without consistent effects on LC ADAM17 protein expression or LC numbers. Anti-IFNAR-mediated LC ADAM17 sheddase function restoration is associated with reduced photosensitive responses that are dependent on EGFR signaling and LC ADAM17. Reactive oxygen species (ROS) is a known mediator of ADAM17 activity; we show that UVR-induced LC ROS production is reduced in lupus model mice, restored by anti-IFNAR, and is cytoplasmic in origin. Our findings suggest that IFN-I promotes photosensitivity at least in part by inhibiting UVR-induced LC ADAM17 sheddase function and raise the possibility that anifrolumab ameliorates lupus skin disease in part by restoring this function. This work provides insight into IFN-I-mediated disease mechanisms, LC regulation, and a potential mechanism of action for anifrolumab in lupus.

Glutathione plays a pivotal role in protecting plants from environmental stresses, oxidative stress, xenobiotics, and some heavy metals. Arabidopsis plants treated with cadmium or copper responded by increasing transcription of the genes for glutathione synthesis, gamma-glutamylcysteine synthetase and glutathione synthetase, as well as glutathione reductase. The response was specific for those metals whose toxicity is thought to be migrated through phytochelatins, and other toxic and nontoxic metals did not alter mRNA levels. Feeding experiments suggested that neither oxidative stress, as results from exposure to H2O2, nor oxidized or reduced glutathione levels were responsible for activating transcription of these genes. Jasmonic acid also activated the same suite of genes, which suggests that it might be involved in the signal transduction pathway for copper and cadmium. Jasmonic acid treatment increased mRNA levels and the capacity for glutathione synthesis but did not alter the glutathione content in unstressed plants, which supports the idea that the glutathione concentration is controlled at multiple levels

Neurological diseases cause physical, psychosocial, and spiritual or existential suffering from the time of their diagnosis. Palliative care focuses on improving quality of life for people with serious illness and their families by addressing this multidimensional suffering. Evidence from clinical trials supports the ability of palliative care to improve patient and caregiver outcomes by the use of outpatient or home-based palliative care interventions for people with motor neuron disease, multiple sclerosis, or Parkinson's disease; inpatient palliative care consultations for people with advanced dementia; telephone-based case management for people with dementia in the community; and nurse-led discussions with decision aids for people with advanced dementia in long-term care. Unfortunately, most people with neurological diseases do not get the support that they need for their palliative care under current standards of healthcare. Improving this situation requires the deployment of routine screening to identify individual palliative care needs, the integration of palliative care approaches into routine neurological care, and collaboration between neurologists and palliative care specialists. Research, education, and advocacy are also needed to raise standards of care.

A mechanically formed electrical nanocontact between gold and tungsten is a prototypical junction between metals with dissimilar electronic structure. Through atomically characterized nanoindentation experiments and first-principles quantum transport calculations, we find that the ballistic conduction across this intermetallic interface is drastically reduced because of the fundamental mismatch between s wave-like modes of electron conduction in the gold and d wave-like modes in the tungsten. The mechanical formation of the junction introduces defects and disorder, which act as an additional source of conduction losses and increase junction resistance by up to an order of magnitude. These findings apply to nanoelectronics and semiconductor device design. The technique that we use is very broadly applicable to molecular electronics, nanoscale contact mechanics, and scanning tunneling microscopy.

A streamlined mini binary vector was constructed that is less than 1/2 the size of the pBIN19 backbone (3.5 kb). This was accomplished by eliminating over 5 kb of non-T-DNA sequences from the pBIN19 vector. The vector still retains all the essential elements required for a binary vector. These include a RK2 replication origin, the nptIII gene conferring kanamycin resistance in bacteria, both the right and left T-DNA borders, and a multiple cloning site (MCS) in between the T-DNA borders to facilitate cloning. Due to the reduced size, more unique restriction sites are available in the MCS, thus allowing more versatile cloning. Since the traF region was not included, it is not possible to mobilize this binary vector into Agrobacterium by triparental mating. This problem can be easily resolved by direct transformation. The mini binary vector has been demonstrated to successfully transform Arabidopsis plants. Based on this mini binary vector, a series of binary vectors were constructed for plant transformation.

The acs1 knockout mutant that has a disruption in the plastidic acetyl-coenzyme A (CoA) synthetase (ACS; At5g36880) gene was used to explore the role of this protein and plastidic acetate metabolism in Arabidopsis (Arabidopsis thaliana). Disruption of the ACS gene decreased ACS activity by 90% and largely blocked the incorporation of exogenous ¹⁴C-acetate and ¹⁴C-ethanol into fatty acids. Whereas the disruption had no significant effect on the synthesis of bulk seed triacylglycerols, the acs1 plants were smaller and flowered later. This suggests that the pyruvate dehydrogenase bypass provided by the aerobic fermentation pathway that converts pyruvate to acetate and probably on to fatty acids is important to the plants during normal growth. The role of ACS in destroying fermentative intermediates is supported by the increased sensitivity of the acs1 mutant to exogenous acetate, ethanol, and acetaldehyde compared to wild-type plants. Whereas these observations suggest that flux through the aerobic fermentation pathway is important, the reason for this flux is unclear. Interestingly, acetate is able to support high rates of plant growth on medium and this growth is blocked in the acs1 mutant.