Miracle-dz/UniFAR-FTUs huggingface dataset:
Paraburkholderia sabiae Uses One Type VI Secretion System (T6SS-1) as a Powerful Weapon against Notorious Plant Pathogens

Rhizobia often display additional beneficial traits such as the production of plant hormones and the acquisition of limited essential nutrients that improve plant growth and enhance plant yields. Here, we show that the rhizobial strain P. sabiae antagonizes important phytopathogens such as P. carotovorum, P. syringae, and R. solanacearum and that this effect is due to contact-dependent killing mediated by one of two T6SS systems identified in the complete, de novo assembled genome sequence of P. sabiae. ABSTRACT Paraburkholderia sabiae LMG24235 is a nitrogen-fixing betaproteobacterium originally isolated from a root nodule of Mimosa caesalpiniifolia in Brazil. We show here that this strain effectively kills strains from several bacterial families (Burkholderiaceae, Pseudomonadaceae, Enterobacteriaceae) which include important plant pathogens in a contact-dependent manner. De novo assembly of the first complete genome of P. sabiae using long sequencing reads and subsequent annotation revealed two gene clusters predicted to encode type VI secretion systems (T6SS), which we named T6SS-1 and T6SS-3 according to previous classification methods (G. Shalom, J. G. Shaw, and M. S. Thomas, Microbiology, 153:2689–2699, 2007, https://doi.org/10.1099/mic.0.2007/006585-0). We created P. sabiae with mutations in each of the two T6SS gene clusters that abrogated their function, and the T6SS-1 mutant was no longer able to outcompete other strains in a contact-dependent manner. Notably, our analysis revealed that T6SS-1 is essential for competition against several important plant pathogens in vitro, including Burkholderia plantarii, Ralstonia solanacearum, Pseudomonas syringae, and Pectobacterium carotovorum. The 9-log reduction in P. syringae cells in the presence of P. sabiae was particularly remarkable. Importantly, in an in vivo assay, P. sabiae was able to protect potato tubers from bacterial soft rot disease caused by P. carotovorum, and this protection was partly dependent on T6SS-1. IMPORTANCE Rhizobia often display additional beneficial traits such as the production of plant hormones and the acquisition of limited essential nutrients that improve plant growth and enhance plant yields. Here, we show that the rhizobial strain P. sabiae antagonizes important phytopathogens such as P. carotovorum, P. syringae, and R. solanacearum and that this effect is due to contact-dependent killing mediated by one of two T6SS systems identified in the complete, de novo assembled genome sequence of P. sabiae. Importantly, co-inoculation of Solanum tuberosum tubers with P. sabiae also resulted in a drastic reduction of soft rot caused by P. carotovorum in an in vivo model system. This result highlights the protective potential of P. sabiae against important bacterial plant diseases, which makes it a valuable candidate for application as a biocontrol agent. It also emphasizes the particular potential of rhizobial inoculants that combine several beneficial effects such as plant growth promotion and biocontrol for sustainable agriculture.
Applying Hierarchical Clustering to Broad Absorption Line Proﬁles for Quasar Classiﬁcation

The region immediately surrounding an actively accreting supermassive black hole at the centre of a massive galaxy, the accretion disk, produces an enormous amount of radiation resulting in a luminous, short-lived phenomenon called a quasar. About 20% of quasars show broad, blue-shifted absorption features in their UV spectra, indicative of an outflowing wind from the accretion disk. These winds can remove angular momentum from the accretion disk, thereby contributing to the growth of the central black hole. Understanding these winds will help us to better constrain the details of how black holes grow during the quasar phase. The structures of the absorption features are sensitive to the properties (ionization state, velocity profile, and thickness) of the winds. Consequently, the broad absorption line profiles of these objects show great diversity in depth and velocity width. Using a sample of 1, 084 broad absorption line quasar spectra from the Sloan Digital Sky Survey, we apply an agglomerative hierarchical clustering algorithm to group spectra by similar C iv absorption line shapes. For each cluster, we compose median spectra and compare the shapes of the C iv broad absorption lines with the properties of prominent, broad emission lines. In agreement with results in the literature, low-velocity, deep troughs are found preferentially in objects for which the radiation from the accretion disk is more energetic. The link between broad absorption line properties and those of emission lines holds promise for allowing us to constrain the structure and dynamics of the outflowing winds.
The human NTG model of migraine in drug discovery and development

ABSTRACT Introduction Various triggers can originate a migraine attack. In healthy volunteers and patients with migraine, the nitroglycerin (NTG) provocation model induces a headache that resembles migraine in pain characteristics and vascular manifestations. This headache is reversible and treatable in monitored conditions, providing an opportunity to test novel antimigraine medications in early clinical development. Areas covered This perspective covers the main characteristics and applications of the human NTG model of migraine with effective and ineffective antimigraine therapies. Expert opinion The NTG model represents a potential de-risking strategy to test novel hypotheses for antimigraine mechanisms in humans. Considering previous studies conducted with effective and ineffective antimigraine therapies, the sensitivity of the model was 71% while the specificity was 100%. The probability that following an analgesic effect, that compound would truly be efficacious in individuals with migraine was 100%. Following a negative result, the probability that such compound would truly be ineffective in patients with individuals was 33%. A clinical trial testing the analgesic properties of novel compounds after a sublingual and/or intravenous NTG challenge in migraine patients may support a subsequent phase 2 trial for the treatment of migraine.
A Bayesian Approach for Detection of Isotropy Violation of a Random Field Over a Sphere

We present a general method for estimating the isotropy violation of random fields on a sphere using a Bayesian formalism. We use Bipolar Spherical Harmonic (BipoSH) representation of general covariance structure on the sphere. Our approach promises to provide a robust quantitative evaluation of the evidence for SI violation-related anomalies in the CMB sky by estimating the BipoSH spectra along with their complete posterior.
Extended Reality Use in Paediatric Intensive Care: A Scoping Review

Background: Extended reality (XR) technology such as virtual and augmented reality is increasingly being utilised in paediatric medicine due to its role in medical education and reported positive impacts on outcomes including pain, anxiety, and sleep. To the author’s knowledge, no previous reviews investigating the use of XR in paediatric intensive care have been undertaken. Objectives: To scope the use of XR in paediatric intensive care, and assess its barriers to adoption, including safety considerations, cleaning and infection control. Eligibility criteria: All articles of any methodological design discussing the use of XR within paediatric intensive and critical care were included. Sources of evidence: Four databases (EMBASE, CINAHL, PsychInfo, PubMed) and Google Scholar were searched without any limitations on publication year. Charting methods: Data was extracted into Microsoft Excel by two authors independently (AG & SF) and cross-checked for completeness. Results: One hundred and eighty-eight articles were originally identified. Following the application of eligibility criteria 16 articles utilising XR in clinical interventions (n = 7) and medical education (n = 9) were included. Articles utilised VR and AR for highly variable purposes within both medical education (eg disaster preparedness, intubation) and clinical interventions (eg decrease pain, nausea, anxiety and improve Glasgow Coma Scale). Conclusions: While research into the use of XR in paediatric intensive care is still in its infancy it has increased dramatically over the past 5 years within two key areas. Firstly, in healthcare education, to assist in the acquisition of PICU-specific knowledge and practice of skills such as intubation of difficult airways. Secondly, studies have evaluated and demonstrated that with appropriate use, VR appears to be a safe and feasible intervention to decrease pain and anxiety in PICU patients.
An Ontology-Based Approach to Improving Medication Appropriateness in Older Patients: Algorithm Development and Validation Study

Background Inappropriate medication in older patients with multimorbidity results in a greater risk of adverse drug events. Clinical decision support systems (CDSSs) are intended to improve medication appropriateness. One approach to improving CDSSs is to use ontologies instead of relational databases. Previously, we developed OntoPharma—an ontology-based CDSS for reducing medication prescribing errors. Objective The primary aim was to model a domain for improving medication appropriateness in older patients (chronic patient domain). The secondary aim was to implement the version of OntoPharma containing the chronic patient domain in a hospital setting. Methods A 4-step process was proposed. The first step was defining the domain scope. The chronic patient domain focused on improving medication appropriateness in older patients. A group of experts selected the following three use cases: medication regimen complexity, anticholinergic and sedative drug burden, and the presence of triggers for identifying possible adverse events. The second step was domain model representation. The implementation was conducted by medical informatics specialists and clinical pharmacists using Protégé-OWL (Stanford Center for Biomedical Informatics Research). The third step was OntoPharma-driven alert module adaptation. We reused the existing framework based on SPARQL to query ontologies. The fourth step was implementing the version of OntoPharma containing the chronic patient domain in a hospital setting. Alerts generated from July to September 2022 were analyzed. Results We proposed 6 new classes and 5 new properties, introducing the necessary changes in the ontologies previously created. An alert is shown if the Medication Regimen Complexity Index is ≥40, if the Drug Burden Index is ≥1, or if there is a trigger based on an abnormal laboratory value. A total of 364 alerts were generated for 107 patients; 154 (42.3%) alerts were accepted. Conclusions We proposed an ontology-based approach to provide support for improving medication appropriateness in older patients with multimorbidity in a scalable, sustainable, and reusable way. The chronic patient domain was built based on our previous research, reusing the existing framework. OntoPharma has been implemented in clinical practice and generates alerts, considering the following use cases: medication regimen complexity, anticholinergic and sedative drug burden, and the presence of triggers for identifying possible adverse events.
Extracorporeal photopheresis induces NETosis in neutrophils derived from patients with chronic graft‐vs‐host disease

Extracorporeal photopheresis (ECP) is considered an effective treatment for patients with chronic graft vs host disease (cGVHD) and demonstrates efficacy in ameliorating GVHD. The mechanism by which ECP acts against cGVHD is not fully understood. Preliminary observations have hinted at the potential involvement of neutrophil extracellular traps (NETs) formation in the pathogenesis of cGVHD. We aimed to assess the influence of ECP on the formation of NETs in patients with cGVHD as a potential mechanism in this setting.
Ribosome Profiling in the Model Diatom Thalassiosira pseudonana

Diatoms are an important group of eukaryotic microalgae, which play key roles in marine biochemical cycling and possess significant biotechnological potential. Despite the importance of diatoms, their regulatory mechanisms of protein synthesis at the translational level remain largely unexplored. Here, we describe the detailed development of a ribosome profiling protocol to study translation in the model diatom Thalassiosira pseudonana, which can easily be adopted for other diatom species. To isolate and sequence ribosome‐protected mRNA, total RNA was digested, and the ribosome‐protected fragments were obtained by a combination of sucrose‐cushion ultracentrifugation and polyacrylamide gel electrophoresis for size selection. To minimize rRNA contamination, a subtractive hybridization step using biotinylated oligos was employed. Subsequently, fragments were converted into sequencing libraries, enabling the global quantification and analysis of changes in protein synthesis in diatoms. The development of this novel ribosome profiling protocol represents a major expansion of the molecular toolbox available for diatoms and therefore has the potential to advance our understanding of the translational regulation in this important group of phytoplankton. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.
The Second Quantized Approach to the Study of Model Hamiltonians in Quantum Hall Regime

OF THE DISSERTATION The Second Quantized Approach to the Study of Model Hamiltonians in Quantum Hall Regime by Li Chen Doctor of Philosophy in Physics Washington University in St. Louis, 2016 Professor Alexander Seidel, Chair The study of model Hamiltonians, whose exact ground states are well known quantum Hall states, have been investigated solely in the literature from the point of view of first quantized approach in the last few decades. However, a second quantized approach to such Hamiltonians has not been taken in the same measure. In this dissertation, we study Haldane pseudopotential, which is the parent Hamiltonian of 1/M Laughlin state, and Trugman-Kivelson pseudopotential, which is the parent Hamiltonian of 2/5 unprojected Jain state. We find that the study of these Hamiltonians in their second quantized forms not only reproduces all properties of their zero modes already known in first quantized approach, but also sheds lights on general studies of such structures of these Hamiltonians as frustration free lattice Hamiltonians.
Evolution of emission line properties and metallicities of star-forming galaxies up to z ~ 3

Until recently, obtaining rest-frame optical spectra of galaxies at z > 1 was a time consuming and challenging observation due to the difficult nature of nearinfrared (near-IR) spectroscopy. However, with the advent of second generation ground-based near-IR spectrographs (e.g. KMOS, MOSFIRE), and the new low resolution near-IR grisms on the Hubble Space Telescope (HST), we have entered a new era in the study of high redshift galaxies. This thesis explores the physical properties of star-forming galaxies in the redshift range 1 < z < 3 by utilising a custom reduction of the 3D-HST near-IR grism spectroscopic survey. One of the most important observational constraints on the evolution of galaxies is the mass-metallicity relation (MZR), which is sensitive to both the star-formation history and various inflow/outflow processes. I use the 3D-HST spectra to provide a new constraint on the MZR at 2.0 < z < 2.3, and moreover measure the O/H abundance directly from the oxygen and hydrogen emission lines ([OII], [OIII] and Hβ) as opposed to the more common method at high redshift of inferring O/H from the N/H ratio (via [NII] and Hα). I show that the traditional form of the MZR is recovered from the 3D-HST data, with metallicity increasing with the stellar mass of a galaxy. However, the absolute metallicity values I derive are inconsistent with previous N/H-based measurements of metallicity at these redshifts. Moreover, I show that the 3D-HST data is inconsistent with the ‘fundamental metallicity relation’ (FMR), and that, contrary to previous claims, this local Universe relation may not hold out to z & 2. To investigate this metallicity discrepancy further, I measure the evolution of the [OIII]/Hβ nebular emission line ratio in the 3D-HST spectra over the redshift range 1.3 < z < 2.3. I compare this observed line ratio evolution with state-ofthe-art theoretical models which take into account the independent evolution of the ionization parameter, electron density and metallicity of star-forming regions with redshift. The homogeneous 3D-HST dataset allows me to perform
Construction and application of microneedle-mediated photothermal therapy and immunotherapy combined anti-tumor drug delivery system

Abstract Conventional treatments for tumors were frequently accompanied by drawbacks and side effects. It might be useful to use the revolutionary microneedle technology which combines photothermal therapy with tumor immunotherapy. In this study, we created a microneedle drug delivery system with mercapto-modified gold nanorods and immune checkpoint blocker anti-PD-1 polypeptide. With good mechanical strength, the microneedle system can efficiently penetrate the skin and deliver drugs. When inserted into human skin, anti-PD-1 peptides and gold nanorods can be released, boosting the capacity of cytotoxic T lymphocytes to destroy tumor cells. Additionally, the elimination of the tumor is aided by the production of heat while being exposed to near-infrared light. This microneedle drug delivery system can enhance the immunological reaction and prolong the survival time of mice. Moreover, it has been demonstrated that the system has mild toxic and side effects on normal tissues and can effectively inhibit the growth of tumors, indicating a bright prospect for the treatment of cancers. GRAPHICAL ABSTRACT
Acute Exercise Increases NK Cell Mitochondrial Respiration and Cytotoxicity against Triple-Negative Breast Cancer Cells under Hypoxic Conditions

ABSTRACT Purpose Triple-negative breast cancer (TNBC) is an aggressive, highly metastatic malignancy with high recurrence rates. Hypoxia is a hallmark of the TNBC tumor microenvironment, which promotes tumor growth while impairing natural killer (NK) cell cytotoxic functions. Although acute exercise improves NK cell function under normoxic conditions, the effect of exercise on NK cell cytotoxic functions under hypoxic conditions mimicking O2 tensions observed in solid tumors is unknown. Methods The cytotoxic functions of resting and postexercise NK cells isolated from thirteen young inactive healthy women were assessed against breast cancer cells expressing different levels of hormone receptors (MCF-7 and MDA-MB-231) under normoxic and hypoxic conditions. Mitochondrial respiration and H2O2 efflux rates of the TNBC-activated NK cells were assessed via high-resolution respirometry. Results Under hypoxia, postexercise NK cells exhibited greater killing of TNBC than resting NK cells. Further, postexercise NK cells were more likely to kill TNBC under hypoxia than normoxic conditions. In addition, mitochondrial respiration associated with oxidative (OXPHOS) capacity of TNBC-activated NK cells was greater in postexercise cells than resting cells under normoxia, but not under hypoxia. Finally, acute exercise was associated with reduced mitochondrial H2O2 efflux by NK cells in both conditions. Conclusions Together, we present crucial interrelationships between hypoxia and exercise-induced changes in NK cell functions against TNBC cells. By modulating their mitochondrial bioenergetic functions, we postulate that acute exercise improves NK cell function under hypoxic conditions. Specifically, NK cell O2 and H2O2 flow (pmol·s−1·million NK cells−1) changes in response to 30-min cycling suggest that exercise primes NK cell tumor killing by reducing mitochondrial oxidative stress and, thus, rescuing their function when exposed to harsh hypoxic environments as observed in the microenvironment of breast solid tumors.
Matrix metalloproteinases are key targets of acupuncture in the treatment of ulcerative colitis

The aim of this study was to elucidate the key targets of acupuncture in the colon of ulcerative colitis (UC) mice model using full-length transcriptome sequencing. 2.5% dextran sodium sulfate (DSS)–induced colitis mice were treated with or without acupuncture. Intestinal pathology was observed, and full transcriptome sequencing and bioinformatic analysis were performed. The results demonstrated that acupuncture treatment reduced the UC symptoms, disease activity index score, and histological colitis score and increased body weight, colon length, and the number of intestinal goblet cells. In addition, acupuncture can also decrease the expression of necrotic biomarker phosphorylates mixed lineage kinase domain-like pseudo kinase (p-MLKL). Full-length transcriptome analysis indicated that acupuncture reversed the expression of 987 of the 1918 upregulated differentially expressed genes (DEGs), and 632 of the 1351 downregulated DEGs induced by DSS. DEGs regulated by acupuncture were mainly involved in inflammatory responses and intestinal barrier pathways. The protein–protein interaction network analysis revealed that matrix metalloproteinases (MMPs) are important genes regulated by acupuncture. Gene set enrichment analysis revealed that extracellular matrix (ECM)–receptor interaction was an important target of acupuncture. In addition, alternative splicing analysis suggested that acupuncture improved signaling pathways related to intestinal permeability, the biological processes of xenobiotics, sulfur compounds, and that monocarboxylic acids are closely associated with MMPs. Overall, our transcriptome analysis results indicate that acupuncture improves intestinal barrier function in UC through negative regulation of MMPs expression.
Comparative reproduction of the female horse, elephant and rhinoceros: implications for advancing assisted reproductive technologies

Recent loss of rhinoceros subspecies has renewed interest in using more advanced assisted reproductive technologies (ART) in rhinoceroses and elephants. Currently, only semen collection, semen preservation and artificial insemination (AI) have been used repeatedly with success in these species. Although ovum pick-up (OPU) and intra-cytoplasmic sperm injection (ICSI) have been reported recently in rhinoceroses, the techniques are not yet optimised. In contrast, multiple ART applications are routinely used in the horse. Since elephants and rhinoceroses share some reproductive features with equids, we postulate that procedures such as OPU, ICSI, in vitro fertilisation (IVF) and embryo transfer (ET), which are well established in the horse, may represent a basis to develop protocols for endangered pachyderms. In this review, we summarise current knowledge on reproductive physiology relevant to ART. We discuss the current state of ART in all three families and the requirements for the successful implementation of OPU, ICSI, IVF and ET in these species. Lay summary Wild rhinoceros and elephant populations are facing ongoing threats; therefore, additional measures are required to protect these species for future generations. Assisted reproductive technologies (ART) include the collection of semen to directly inseminate females or to fertilise oocytes (eggs) in a laboratory to produce embryos, which can be transferred into a recipient female at a later date. While these techniques are routinely used in humans and domestic animals such as the horse, more research is needed to incorporate such technologies into the breeding of elephants and rhinoceroses. As the horse is the closest related domestic species to the rhinoceros, it may serve as the best possible role model. We discuss the current state of ART in the horse, elephant and rhinoceros and the possibilities for future use of these techniques in breeding such endangered animals.