The biosynthesis of isoprenoids in plant cells occurs from precursors produced in the cytosol by the mevalonate （MVA） pathway and in the plastid by the methylerythritol 4-phosphate （MEP） pathway, but ...little is known about the mechanisms coordinating both pathways. Evidence of the importance of sugar signaling for such coordination in Arabi- dopsis thaliana is provided here by the characterization of a mutant showing an increased accumulation of MEP-derived isoprenoid products （chlorophylls and carotenoids） without changes in the levels of relevant MEP pathway transcripts, proteins, or enzyme activities. This mutant was found to be a new loss-of-function allele of PRL1 （Pleiotropic Regulatory Locus 1）, a gene encoding a conserved WD-protein that functions as a global regulator of sugar, stress, and hormone responses, in part by inhibition of SNFl-related protein kinases （SnRK1）. Consistent with the reported role of SnRK1 kinases in the phosphorylation and inactivation of the main regulatory enzyme of the MVA p
CASE-BASED TEACHING AND LEARNING EXPERIENCES Mary Durand Thomas, Frederica W. O'Connor, Marilynn L. Albert, Doris Boutain, Patricia A. Brandt
Issues in mental health nursing,
20/1/1/, Letnik:
22, Številka:
5
Journal Article
Recenzirano
Case-based teaching and learning strategies can be utilized to assist advanced practice psychiatric nursing students in both obtaining requisite knowledge and enhancing clinical reasoning skills. We ...discuss the benefits of case-based learning in terms of how it (1) contributes to students' appropriate organization of information to be recalled later for use in clinical reasoning situations; (2) generates experiences that students would not otherwise have; (3) increases the visibility of students' clinical reasoning processes; and (4) enhances students' confidence. This article also explores three examples of case-based teaching and learning: use of written cases in a seminar; use of standardized patients in an assessment course; and utilization of web-based cases for learning assessment and intervention skills. Finally, we compare and contrast each of these methods in terms of their relative effectiveness in achieving each of the benefits.
Lipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a ...protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD-bacterial contacts. Thus, LDs actively participate in mammalian innate immunity at two levels: They are both cell-autonomous organelles that organize and use immune proteins to kill intracellular pathogens as well as central players in the local and systemic metabolic adaptation to infection.
A recombinant SARS-CoV-2 spike protein nanoparticle vaccine delivered in the deltoid muscle on days 0 and 21 was found to be immunogenic at both 5 μg and 25 μg doses. When given with a saponin-based ...adjuvant, both doses were equally immunogenic, with little or no reactogenicity, and elicited neutralizing antibody titers higher than those in convalescent serum.
Interest surrounding generative large language models (LLMs) has rapidly grown. Although ChatGPT (GPT-3.5), a general LLM, has shown near-passing performance on medical student board examinations, ...the performance of ChatGPT or its successor GPT-4 on specialized examinations and the factors affecting accuracy remain unclear. This study aims to assess the performance of ChatGPT and GPT-4 on a 500-question mock neurosurgical written board examination.
The Self-Assessment Neurosurgery Examinations (SANS) American Board of Neurological Surgery Self-Assessment Examination 1 was used to evaluate ChatGPT and GPT-4. Questions were in single best answer, multiple-choice format. χ 2 , Fisher exact, and univariable logistic regression tests were used to assess performance differences in relation to question characteristics.
ChatGPT (GPT-3.5) and GPT-4 achieved scores of 73.4% (95% CI: 69.3%-77.2%) and 83.4% (95% CI: 79.8%-86.5%), respectively, relative to the user average of 72.8% (95% CI: 68.6%-76.6%). Both LLMs exceeded last year's passing threshold of 69%. Although scores between ChatGPT and question bank users were equivalent ( P = .963), GPT-4 outperformed both (both P < .001). GPT-4 answered every question answered correctly by ChatGPT and 37.6% (50/133) of remaining incorrect questions correctly. Among 12 question categories, GPT-4 significantly outperformed users in each but performed comparably with ChatGPT in 3 (functional, other general, and spine) and outperformed both users and ChatGPT for tumor questions. Increased word count (odds ratio = 0.89 of answering a question correctly per +10 words) and higher-order problem-solving (odds ratio = 0.40, P = .009) were associated with lower accuracy for ChatGPT, but not for GPT-4 (both P > .005). Multimodal input was not available at the time of this study; hence, on questions with image content, ChatGPT and GPT-4 answered 49.5% and 56.8% of questions correctly based on contextual context clues alone.
LLMs achieved passing scores on a mock 500-question neurosurgical written board examination, with GPT-4 significantly outperforming ChatGPT.
The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and its numerous spike mutations, which have the potential to evade neutralizing ...antibodies elicited by COVID-19 vaccines. Here we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants who had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that a heterologous CoronaVac prime vaccination of two doses followed by a BNT162b2 booster induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and the Delta variant, resembling the titers obtained after two doses of mRNA vaccines. Although neutralization of Omicron was undetectable in participants who had received a two-dose regimen of CoronaVac, the BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron compared with the two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 7.1-fold and 3.6-fold for Omicron compared with the ancestral strain and the Delta variant, respectively. These findings have immediate implications for multiple countries that previously used a CoronaVac regimen and reinforce the idea that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.
Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous ...thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Throughout the bacterial domain, the alarmone ppGpp dramatically reprograms transcription following nutrient limitation. This “stringent response” is critical for survival and antibiotic tolerance ...and is a model for transcriptional regulation by small ligands. We report that ppGpp binds to two distinct sites 60 Å apart on E. coli RNA polymerase (RNAP), one characterized previously (site 1) and a second identified here at an interface of RNAP and the transcription factor DksA (site 2). The location and unusual tripartite nature of site 2 account for the DksA-ppGpp synergism and suggest mechanisms for ppGpp enhancement of DksA’s effects on RNAP. Site 2 binding results in the majority of ppGpp’s effects on transcription initiation in vitro and in vivo, and strains lacking site 2 are severely impaired for growth following nutritional shifts. Filling of the two sites at different ppGpp concentrations would expand the dynamic range of cellular responses to changes in ppGpp levels.
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•ppGpp still regulates a DksA-RNAP complex lacking the known ppGpp binding site•A ppGpp binding site forms at the DksA-RNAP interface, ∼60 Å from the first site•ppGpp binding to this second site strongly affects transcription in vitro and in vivo•Cells lacking both sites have dramatic defects in recovery from nutritional shifts
To survive starvation, bacteria reprogram their transcriptomes by producing ppGpp, a signaling molecule that coordinates the stringent response by regulating hundreds of promoters. Unexpectedly, there are two widely separated ppGpp binding sites on RNA polymerase required for regulation. Cells lacking both sites are severely limited for adaptation to nutritional changes.
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