Mitochondrial complex I subunit NDUFS8.2 modulates responses to stresses associated with reduced water availability.

Mitochondria are important sources of energy in plants and are implicated in coordination of a number of metabolic and physiological processes including stabilization of redox balance, synthesis and turnover of a number of metabolites, and control of programmed cell death. Mitochondrial electron transport chain (mETC) is the backbone of the energy producing process which can influence other processes as well. Accumulating evidence suggests that mETC can affect responses to environmental stimuli and modulate tolerance to extreme conditions such as drought or salinity. Screening for stress responses of 13 Arabidopsis mitochondria-related T-DNA insertion mutants, we identified ndufs8.2-1 which has an increased ability to withstand osmotic and oxidative stresses compared to wild type plants. Insertion in ndufs8.2-1 disrupted the gene that encodes the NADH dehydrogenase [ubiquinone] fragment S subunit 8 (NDUFS8) a component of Complex I of mETC. ndufs8.2-1 tolerated reduced water availability, retained photosynthetic activity and recovered from severe water stress with higher efficiency compared to wild type plants. Several mitochondrial functions were altered in the mutant including oxygen consumption, ROS production, ATP and ADP content as well as activities of genes encoding alternative oxidase 1A (AOX1A) and various alternative NAD(P)H dehydrogenases (ND). Our results suggest that in the absence of NDUFS8.2 stress-induced ROS generation is restrained leading to reduced oxidative damage and improved tolerance to water deficiency. mETC components can be implicated in redox and energy homeostasis and modulate responses to stresses associated with reduced water availability.

Paramedic Education and Training for the Management of Patients Presenting with Low-Acuity Clinical Conditions: A Scoping Review.

Ambulance services around the world are increasingly attending to calls for non-emergency conditions. These lower-acuity conditions do not always require patients to be transported to the emergency department. Consequently, over the past two decades, ambulance services have implemented strategies to support paramedics in diverting non-urgent patients to alternative care pathways. However, assessing and managing low-acuity conditions can be challenging for paramedics, especially when education and training has traditionally focussed on emergency care. This scoping review explores the education and training provided to paramedics on low-acuity clinical conditions and the use of alternative care pathways. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews was applied. The databases searched included Scopus, CINAHL, Embase, Emcare, and MEDLINE (PubMed). The search identified one-hundred sixty-six records, with a total of nine articles reviewed after the removal of duplicates and the screening process. The articles were diverse, with education and training ranging from university degrees for extended care practitioners to short in-service-based training for a suite of protocols or assessment tools. However, the literature addressing education and training on low-acuity conditions and alternative care pathways is limited, with the type and length of education programs appearing to influence practice. There is a need for further research to establish a low acuity education model.

Genome-scale metabolic models reveal determinants of phenotypic differences in non-Saccharomyces yeasts.

BACKGROUND: Use of alternative non-Saccharomyces yeasts in wine and beer brewing has gained more attention the recent years. This is both due to the desire to obtain a wider variety of flavours in the product and to reduce the final alcohol content. Given the metabolic differences between the yeast species, we wanted to account for some of the differences by using in silico models. RESULTS: We created and studied genome-scale metabolic models of five different non-Saccharomyces species using an automated processes. These were: Metschnikowia pulcherrima, Lachancea thermotolerans, Hanseniaspora osmophila, Torulaspora delbrueckii and Kluyveromyces lactis. Using the models, we predicted that M. pulcherrima, when compared to the other species, conducts more respiration and thus produces less fermentation products, a finding which agrees with experimental data. Complex I of the electron transport chain was to be present in M. pulcherrima, but absent in the others. The predicted importance of Complex I was diminished when we incorporated constraints on the amount of enzymatic protein, as this shifts the metabolism towards fermentation. CONCLUSIONS: Our results suggest that Complex I in the electron transport chain is a key differentiator between Metschnikowia pulcherrima and the other yeasts considered. Yet, more annotations and experimental data have the potential to improve model quality in order to increase fidelity and confidence in these results. Further experiments should be conducted to confirm the in vivo effect of Complex I in M. pulcherrima and its respiratory metabolism.

Paramedic Education to Support the Use of Low-Acuity Care Pathways: A Scoping Review Protocol.

Ambulance services worldwide have transformed over time into health care services that not only attend to life-threatening emergencies, but are also increasingly being utilised for patients with low-acuity or non-urgent illness and injury. As a result, there has been a need to adapt and include mechanisms to assist paramedics in the assessment and management of such patients, including alternative pathways of care. However, it has been identified that education and training for paramedics in the care of low-acuity patients is limited. This study aims to identify potential gaps in the literature and inform further research, paramedic education and training, patient care guidelines, and policy. A scoping review will be conducted utilising the Joanna Briggs Institutes methodology. A range of relevant electronic databases will be searched along with the grey literature, using search terms related to paramedic education for low-acuity patient care pathways. The search results will be screened by two authors and presented in the PRISMA-ScR format, with articles presented in tabular format and analysed thematically. The results of this scoping review will inform further research exploring paramedic education, clinical guidelines, policy and experiences in the management of low-acuity patients.

Stakeholder perspectives of piloting pre-hospital COVID-19 lateral flow testing and direct admissions pathway: exploring why well-received ideas have low uptake.

Introduction: In January 2021, Yorkshire Ambulance Service and Hull University Teaching Hospitals implemented a pilot COVID-19 lateral flow testing (LFT) and direct admissions pathway to assess the feasibility of using pre-hospital LFTs to bypass the emergency department. Due to lower than anticipated uptake of the pilot among paramedics, we undertook a process evaluation to assess reasons for low uptake and perceived potential benefits and risks associated with the pilot. Methods: We undertook semi-structured telephone interviews with 12 paramedics and hospital staff. We aimed to interview paramedics who had taken part in the pilot, those who had received the project information but not taken part and ward staff receiving patients from the pilot. We transcribed interviews verbatim and analysed data using thematic analysis. Results: Participation in the pilot appeared to be positively influenced by high personal capacity for undertaking research (being 'research-keen') and negatively influenced by 'COVID-19 exhaustion', electronic information overload and lack of time for training. Barriers to use of the pathway related to 'poor timing' of the pilot, restrictive patient eligibility and inclusion criteria. The rapid rollout meant that paramedics had limited knowledge or awareness of the pilot, and pilot participants reported poor understanding of the pilot criteria or the rationale for the criteria. Participants who were involved in the pilot were overwhelmingly positive about the intervention, which they perceived as having limited risks and high potential benefits to the health service, patients and themselves, and supported future roll-out. Conclusions: Ambulance clinician involvement in rapid research pilots may be improved by using multiple recruitment methods (electronic and other), providing protected time for training and increased direct support for paramedics with lower personal capacity for research. Improved communication (including face-to-face approaches) may help understanding of eligibility criteria and increase appropriate recruitment.

Differentiating between the sequence of structural events on alternative pathways of folding of a heterodimeric protein.

Distinguishing between competing pathways of folding of a protein, on the basis of how they differ in their progress of structure acquisition, remains an important challenge in protein folding studies. A previous study had shown that the heterodimeric protein, double chain monellin (dcMN) switches between alternative folding pathways upon a change in guanidine hydrochloride (GdnHCl) concentration. In the current study, the folding of dcMN has been characterized by the pulsed hydrogen exchange (HX) labeling methodology used in conjunction with mass spectrometry. Quantification of the extent to which folding intermediates accumulate and then disappear with time of folding at both low and high GdnHCl concentrations, where the folding pathways are known to be different, shows that the folding mechanism is describable by a triangular three-state mechanism. Structural characterization of the productive folding intermediates populated on the alternative pathways has enabled the pathways to be differentiated on the basis of the progress of structure acquisition that occurs on them. The intermediates on the two pathways differ in the extent to which the α-helix and the rest of the ß-sheet have acquired structure that is protective against HX. The major difference is, however, that ß2 has not acquired any protective structure in the intermediate formed on one pathway, but it has acquired significant protective structure in the intermediate formed on the alternative pathway. Hence, the sequence of structural events is different on the two alternative pathways.

The significance of WRKY45 transcription factor in metabolic adjustments during dark-induced leaf senescence.

Plants are constantly exposed to environmental changes that affect their performance. Metabolic adjustments are crucial to controlling energy homoeostasis and plant survival, particularly during stress. Under carbon starvation, coordinated reprogramming is initiated to adjust metabolic processes, which culminate in premature senescence. Notwithstanding, the regulatory networks that modulate transcriptional control during low energy remain poorly understood. Here, we show that the WRKY45 transcription factor is highly induced during both developmental and dark-induced senescence. The overexpression of Arabidopsis WRKY45 resulted in an early senescence phenotype characterized by a reduction of maximum photochemical efficiency of photosystem II and chlorophyll levels in the later stages of darkness. The detailed metabolic characterization showed significant changes in amino acids coupled with the accumulation of organic acids in WRKY45 overexpression lines during dark-induced senescence. Furthermore, the markedly upregulation of alternative oxidase (AOX1a, AOX1d) and electron transfer flavoprotein/ubiquinone oxidoreductase (ETFQO) genes suggested that WRKY45 is associated with a dysregulation of mitochondrial signalling and the activation of alternative respiration rather than amino acids catabolism regulation. Collectively our results provided evidence that WRKY45 is involved in the plant metabolic reprogramming following carbon starvation and highlight the potential role of WRKY45 in the modulation of mitochondrial signalling pathways.

The Alternative Pre-hospital Pathway team: reducing conveyances to the emergency department through patient centered Community Emergency Medicine.

BACKGROUND: Internationally increasing demand for emergency care is driving innovation within emergency services. The Alternative Pre-Hospital Pathway (APP) Team is one such Community Emergency Medicine (CEM) initiative developed in Cork, Ireland to target low acuity emergency calls. In this paper the inception of the APP Team is described, and an observational descriptive analysis of the APP Team's service data presented for the first 12 months of operation. The aim of this study is to describe and analyse the APP team service. METHODS: The APP Team, consisting of a Specialist Registrar (SpR) in Emergency Medicine (EM) and an Emergency Medical Technician (EMT) based in Cork, covers a mixed urban and rural population of approximately 300,000 people located within a 40-min drive time of Cork University Hospital. The team are dispatched to low acuity 112/999 calls, aiming to provide definitive care or referring patients to the appropriate community or specialist service. A retrospective analysis was performed of the team's first 12 months of operation using the prospectively maintained service database. RESULTS: Two thousand and one patients were attended to with a 67.8% non-conveyance rate. The median age was 62 years, with 33.0% of patients aged over 75 years. For patients over 75 years, the non-conveyance rate was 62.0%. The average number of patients treated per shift was 7. Medical complaints (319), falls (194), drug and alcohol related presentations (193), urological (131), and respiratory complaints (119) were the most common presentations. CONCLUSION: Increased demand for emergency care and an aging population is necessitating a re-design of traditional models of emergency care delivery. We describe the Alternative Pre-Hospital Pathway service, delivered by an EMT and an Emergency Medicine SpR responding to low acuity calls. This service achieved a 68% non-conveyance rate; our data demonstrates that a community emergency medicine outreach team in collaboration with the National Ambulance Service offering Alternative Pre-Hospital Pathways is an effective model for reducing conveyances to hospital.

Association of Leukemia Target Genes Tet2, Bcl2, and Slc23a2 in Vitamin C Pathways.

BACKGROUND: Vitamin C has been used in combination with several target genes in the treatment of leukemia. Tet methylcytosine dioxygenase (Tet2), B-cell lymphoma 2 (Bcl2), and solute carrier family 23 member 2 (Slc23a2) are the major target genes in the treatment of leukemia and are relevant to vitamin C. MATERIALS AND METHODS: Using whole-genome expression profiles from mouse livers, the expression quantitative trait locus (eQTL), correlation matrix, and gene network graph were constructed with probes from each of these three genes and with their relative genes. The function of key genes was examined by their pathways and reported information. The results indicated that although direct correlations among their expression levels were not strong, alternative connecting pathways were discovered. By comparing the expression levels of one probe with known sequences from each of the three genes, we identified several key genes, induced myeloid leukemia cell differentiation protein (Mcl1), far upstream element-binding protein 1 (Fubp1), and tumor protein D52-like 2 (Tpd52l2), which play important roles in acute lymphocytic leukemia and acute myelocytic leukemia. In conclusion, Alternative pathways and key genes that connect Tet2, Bcl2, and Slc23a2 for their therapeutic applications with vitamin C were identified.

Commonalities and differences in plants deficient in autophagy and alternative pathways of respiration on response to extended darkness.

Autophagy is a highly conserved cellular mechanism in eukaryotes allowing the degradation of cell constituents. It is of crucial significance in both cellular homeostasis and nutrient recycling. During energy limited conditions plant cells can metabolize alternative respiratory substrates, such as amino acids, providing electrons to the mitochondrial metabolism via the tricarboxylic acid (TCA) cycle or electron transfer flavoprotein/ electron transfer flavoprotein ubiquinone oxidoreductase (ETF/ETFQO) system. Our recent study reveals the importance of autophagy in the supply of amino acids to provide energy through alternative pathways of respiration during carbon starvation. This fact apart, autophagy seems to have more generalized effects related not only to amino acid catabolism but also to metabolism in general. By further comparing the metabolic data obtained with atg mutants with those of mutants involved in the alternative pathways of respiration, we observed clear differences between these mutants, pointing out additional effects of the autophagy deficiency on metabolism of Arabidopsis leaves. Collectively, our data point to an interdependence between mitochondrial metabolism and autophagy and suggest an exquisite regulation of primary metabolism under low energetic conditions.

Referral pathways for patients with TIA avoiding hospital admission: a scoping review.

OBJECTIVE: To identify the features and effects of a pathway for emergency assessment and referral of patients with suspected transient ischaemic attack (TIA) in order to avoid admission to hospital. DESIGN: Scoping review. DATA SOURCES: PubMed, CINAHL Web of Science, Scopus. STUDY SELECTION: Reports of primary research on referral of patients with suspected TIA directly to specialist outpatient services. DATA EXTRACTION: We screened studies for eligibility and extracted data from relevant studies. Data were analysed to describe setting, assessment and referral processes, treatment, implementation and outcomes. RESULTS: 8 international studies were identified, mostly cohort designs. 4 pathways were used by family doctors and 3 pathways by emergency department physicians. No pathways used by paramedics were found. Referrals were made to specialist clinic either directly or via a 24-hour helpline. Practitioners identified TIA symptoms and risk of further events using a checklist including the ABCD2 tool or clinical assessment. Antiplatelet medication was often given, usually aspirin unless contraindicated. Some patients underwent tests before referral and discharge. 5 studies reported reduced incident of stroke at 90 days, from 6-10% predicted rate to 1.3-2.1% actual rate. Between 44% and 83% of suspected TIA cases in these studies were referred through the pathways. CONCLUSIONS: Research literature has focused on assessment and referral by family doctors and ED physicians to reduce hospitalisation of patients with TIA. No pathways for paramedical use were reported. We will use results of this scoping review to inform development of a paramedical referral pathway to be tested in a feasibility trial. TRIAL REGISTRATION NUMBER: ISRCTN85516498. Stage: pre-results.

Mechanisms that increase the growth efficiency of diatoms in low light.

Photoacclimation was studied in Thalassiosira pseudonana to help understand mechanisms underlying the success of diatoms in low-light environments, such as coastal and deep mixing ecosystems. Light harvesting and other cell characteristics were combined with oxygen and carbon production measurements to assess the water-splitting reaction at PSII ([Formula: see text]) and intermediate steps leading to net carbon production (NPPC). These measurements revealed that T. pseudonana is remarkably efficient at converting harvested light energy into biomass, with at least 57 % of [Formula: see text] retained as NPPC across all light-limited growth rates examined. Evidence for upregulation of ATP generation pathways that circumvent carbon fixation indicated that high growth efficiency at low light levels was at least partly due to increases in the efficiency of ATP production. Growth rate-dependent demands for ATP and NADPH were reflected in carbon composition and in unexpected shifts in the light-limited slope (α) of photosynthesis-irradiance relationships generated from chlorophyll-specific (14)C-uptake. Overall, these results suggest that pathway gating of carbon and energy flow depends on light availability and is a key factor promoting the efficiency of diatom growth at low light intensities.

[Alternative oxidase - never ending story]. / Oksydaza alternatywna - niedokonczona opowiesc.

Investigations of plant cyanide resistant respiration lead to the discovery in mitochondrial respiratory chain of the second terminal oxidase, alternative oxidase (AOX). AOX transfers electrons from reduced ubiquinone to oxygen omitting two coupling places thus lowering energetic efficiency of respiration. The presence of AOX was shown in all plants and also in some fungi, mollusca and protista. In termogenic plants the activity of AOX is connected with heat production. In other organisms AOX activity is important for maintaining metabolic homeostasis (carbon metabolism, cell redox state and energy demand) and ROS homeostasis. In this article structure of plant AOX protein and the regulation on molecular levels was described. Possible role of AOX as stress marker was pointed and the possibility of using AOX in human gene therapy was discussed.

NMD mechanism and the functions of Upf proteins in plant.

Nonsense-mediated decay (NMD) mechanism, also called mRNA surveillance, is a universal mRNA degradation pathway in eukaryotes. Hundreds of genes can be regulated by NMD whether in single-celled or higher organisms. There have been many studies on NMD and NMD factors (Upf proteins) with regard to their crucial roles in mRNA decay, especially in mammals and yeast. However, research focusing on NMD in plant is still lacking compared to the research that has been dedicated to NMD in mammals and yeast. Even so, recent study has shown that NMD factors in Arabidopsis can provide resistance against biotic and abiotic stresses. This discovery and its associated developments have given plant NMD mechanism a new outlook and since then, more and more research has focused on this area. In this review, we focused mainly on the distinctive NMD micromechanism and functions of Upf proteins in plant with references to the role of mRNA surveillance in mammals and yeast. We also highlighted recent insights into the roles of premature termination codon location, trans-elements and functions of other NMD factors to emphasize the particularity of plant NMD. Furthermore, we also discussed conventional approaches and neoteric methods used in plant NMD researches.

Exploring the transition experiences of students entering into preregistration nursing degree programs with previous professional nursing qualifications: an integrative review.

AIMS AND OBJECTIVES: This paper aims to investigate the transition experiences of students with previous nursing qualifications (nondegree qualifications) entering a nursing degree program. BACKGROUND: Nurses with professional nursing qualifications (nondegree) are an important pool of professionals to draw on to help address nursing shortages through providing alternative pathways to becoming registered nurses. However, research suggests this cohort need higher levels of support and intervention to be successful. DESIGN: An integrative review was conducted, guided by Whittemore and Knafl's framework. A comprehensive search was conducted and 14 studies were included in the review. METHODS: A five-stage approach was used to conduct the review: problem identification, literature search, data evaluation, data analysis and presentation of results. Constant comparative analysis was used to identify commonalities, differences and themes in the relevant literature. RESULTS: Themes emerged that suggested students struggled with academic and institutional challenges, becoming learners, managing conflicting demands of outside life, developing a student identity and experienced threat to their sense of professional identity. Additionally, the cohort did not view themselves as 'the same' as traditional students. Holland's framework provides a useful framework from which to conceptualise these students' experiences. CONCLUSION: There are challenges for this cohort of students as they transition into degree level study. Supportive activities that extend and further develop students' personality orientations may be a useful starting point in addressing some of the challenges and providing a more positive transition to university. RELEVANCE TO CLINICAL PRACTICE: The demand for health care is growing and there remains a shortfall of registered nurses. Nurses with professional qualifications (nondegree) are an important pool of professionals from which to increase registered nurse numbers and address workforce sustainability issues.

LINKING TIME-DEPENDENT CARBON-FIXATION EFFICIENCIES IN DUNALIELLA TERTIOLECTA (CHLOROPHYCEAE) TO UNDERLYING METABOLIC PATHWAYS(1).

The chl-specific short-term (14) C-based production (P(b) ) measurement is a widely used tool to understand phytoplankton responses to environmental stresses. However, among the metabolic consequences of these stresses is variability in lifetimes of newly fixed carbon that cause P(b) to range between chl-specific net primary production (NPP*) and chl-specific gross photosynthetic electron flow that is available for carbon reduction () depending on growth rate. To investigate the basis for this discrepancy, photosynthate utilization was characterized in Dunaliella tertiolecta Butcher grown at three different growth rates in N-limited chemostats. P(b) was measured throughout a 2 min to 24 h time course and showed clear growth-rate-dependent differences in lifetimes of newly fixed carbon. (14) C pulse-chase experiments revealed differences in patterns of carbon utilization between growth rates. At high growth rate, the majority of (14) C was initially fixed into polysaccharide and lipid, but the relative contribution of each labeled biochemical pool to the total label changed over 24 h. In fast-growing cells, labeled polysaccharides decreased 50%, while labeled lipids increased over the first 4 h. At low growth rate, (14) C was initially incorporated primarily into protein, but the contribution of labeled protein to the total label increased over the next 24 h. Together, time-resolved measurements of P(b) and cellular NAD and NADP content suggest an enhanced role for alternative dissipation pathways at very low growth rate. Findings of this study contribute to an integrated understanding of growth-rate-dependent shifts in metabolic processes from photosynthesis to net growth.