Miracle-dz/UniFAR-FTUs huggingface dataset:
Measurement and analysis of partial lightning currents in a head phantom

Direct lightning strikes to the human head can lead to various effects, ranging from burnings to death. The biological and physical mechanisms of a direct lightning strike in the human head are not well understood. The aim of this paper is to design an experimental setup to measure the spatial and temporal current distribution during a direct lightning strike to physical head phantoms to establish normative values for personal lightning protection equipment design and testing. We created head phantoms made of agarose, replicating the geometric and dielectric properties of scalp, skull, and intracranial volume. The bases of the three compartments were galvanically contacted via copper electrodes to measure the current per compartment. We used pulse generators to apply aperiodic voltage and current signals that modelled lightning components. Our experiments indicated that the scalp compartment was exposed to the current with a fraction of 80–90%. The brain and skull compartments were exposed between 6–13% and 3–6% of the total measured current respectively. In case of a flashover, most of the current (98–99%) flowed through the discharge channel. Unlike previous theoretical estimates and measurements in technical setups, we observed considerably longer times for the flashover to build up. In our experiments, the time to build up a fully formed flashover varied from approximately 30–700 μs. The observed current patterns in cases without and with flashover provided information on regions of possible damage in the human head. Consequently, we identified the phenomenon of a flashover as a potential mechanism for humans to survive a lightning strike. Our measured current distributions and amplitudes formed the base for normative values, which can be used in later experimental investigations regarding the possibilities of individual lightning protection equipment for humans.
JAZ4 is involved in plant defense, growth, and development in Arabidopsis.

JASMONATE ZIM-DOMAIN (JAZ) proteins comprise a family of transcriptional repressors that modulate jasmonate (JA) responses. JAZ proteins form a co-receptor complex with the F-box protein CORONATINE INSENSITIVE1 (COI1) that recognizes both jasmonoyl-L-isoleucine (JA-Ile) and the bacterial-produced phytotoxin coronatine (COR). Although several JAZ family members have been placed in this pathway, the role of JAZ4 in this model remains elusive. In this study, we observed that the jaz4-1 mutant of Arabidopsis is hyper-susceptible to Pseudomonas syringae pv. tomato (Pst) DC3000, while Arabidopsis lines overexpressing a JAZ4 protein lacking the Jas domain (JAZ4∆Jas) have enhanced resistance to this bacterium. Our results show that the Jas domain of JAZ4 is required for its physical interaction with COI1, MYC2 or MYC3, but not with the repressor complex adaptor protein NINJA. Furthermore, JAZ4 degradation is induced by COR in a proteasome- and Jas domain-dependent manner. Phenotypic evaluations revealed that expression of JAZ4∆Jas results in early flowering and increased length of root, hypocotyl, and petiole when compared to Col-0 and jaz4-1 plants, although JAZ4∆Jas lines remain sensitive to MeJA- and COR-induced root and hypocotyl growth inhibition. Additionally, jaz4-1 mutant plants have increased anthocyanin accumulation and late flowering compared to Col-0, while JAZ4∆Jas lines showed no alteration in anthocyanin production. These findings suggest that JAZ4 participates in the canonical JA signaling pathway leading to plant defense response in addition to COI1/MYC-independent functions in plant growth and development, supporting the notion that JAZ4-mediated signaling may have distinct branches.
The role of oxidative stress and hypoxia in renal disease

Oxygen is required to sustain aerobic organisms. Reactive oxygen species (ROS) are constantly released during mitochondrial oxygen consumption for energy production. Any imbalance between ROS production and its scavenger system induces oxidative stress. Oxidative stress, a critical contributor to tissue damage, is well-known to be associated with various diseases. The kidney is susceptible to hypoxia, and renal hypoxia is a common final pathway to end stage kidney disease, regardless of the underlying cause. Renal hypoxia aggravates oxidative stress, and elevated oxidative stress, in turn, exacerbates renal hypoxia. Oxidative stress is also enhanced in chronic kidney disease, especially diabetic kidney disease, through various mechanisms. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of renal injury. This review examines recent evidence connecting chronic hypoxia and oxidative stress in renal disease and subsequently describes several promising therapeutic approaches against oxidative stress.
Daptomycin‐resistant Staphylococcus aureus clinical isolates are poorly sensed by dendritic cells

Methicillin‐resistant Staphylococcus aureus (MRSA) presents an increasing threat to public health, with antimicrobial resistance on the rise and infections endemic in the hospital setting. Despite a global research effort to understand and combat antimicrobial resistance, less work has focused on understanding the nuances in the immunopathogenesis of clinical strains. In particular, there is a surprising gap of knowledge in the literature pertaining to how clinical strains are recognized by dendritic cells (DCs). Here, we show that the activation of DCs is compromised in response to MRSA strains resistant to the last‐line antibiotic daptomycin. We found a significant reduction in the secretion of proinflammatory cytokines including tumor necrosis factor‐α, interleukin‐6, regulated upon activation, normal T cell expressed, and secreted and macrophage inflammatory protein‐1β, as well as decreased expression of CD80 by DCs responding to daptomycin‐resistant MRSA. We further demonstrate that this phenotype is coincident with the acquisition of specific point mutations in the cardiolipin synthase gene cls2, and, partly, in the bifunctional lysylphosphatidylglycerol flippase/synthetase gene mprF, which are genes that are often mutated in clinical daptomycin‐resistant strains. Therefore, throughout infection and antibiotic therapy, MRSA has the capacity to not only develop further antibiotic resistance, but also develop resistance to immunological recognition by DCs, because of single amino acid point mutations occurring under the selective pressures of both host immunity and antibiotic therapy. Understanding the diversity of clinical MRSA isolates and the nuances in their immune recognition will have important implications for future therapeutics and the treatment of these infections.
Two Auxin Response Elements Fine-Tune PINOID Expression During Gynoecium Development in Arabidopsis thaliana

The plant hormone auxin controls almost all aspects of plant development through the gene regulatory properties of auxin response factors (ARFs) which bind so-called auxin responsive elements (AuxREs) in regulatory regions of their target genes. It has been proposed that ARFs interact and cooperate with other transcription factors (TFs) to bind to complex DNA-binding sites harboring cis-elements for several TFs. Complex DNA-binding sites have not been studied systematically for ARF target genes. ETTIN (ETT; ARF3) is a key regulator of gynoecium development. Cooperatively with its interacting partner INDEHISCENT (IND), ETT regulates PINOID (PID), a gene involved in the regulation gynoecium apical development (style development). Here, we mutated two ETT-bound AuxREs within the PID promoter and observed increased style length in gynoecia of plants carrying mutated promoter variants. Furthermore, mutating the AuxREs led to ectopic repression of PID in one developmental context while leading to ectopically upregulated PID expression in another stage. Our data also show that IND associates with the PID promoter in an auxin-sensitive manner. In summary, we demonstrate that targeted mutations of cis-regulatory elements can be used to dissect the importance of single cis-regulatory elements within complex regulatory regions supporting the importance of the ETT-IND interaction for PID regulation. At the same time, our work also highlights the challenges of such studies, as gene regulation is highly robust, and mutations within gene regulatory regions may only display subtle phenotypes.
Expression and Characterization of a Novel α ‐ Amylase from Salinispora arenicola CNP 193

α-Amylases are used in various biotechnological processes including the textile, paper, food, biofuels, detergents and pharmaceutical industries. In this study, a novel gene encoding α-amylase was cloned from marine bacterium Salinispora arenicola CNP193 and the protein was expressed in Escherichia coli. The α-amylase gene from S. arenicola CNP193 had a length of 1839 bp and encoded a α-amylase with an estimated molecular mass of 74 kDa. The optimum temperature and pH for the recombinant α-amylase was 50 °C and 7 respectively. Na+, K+ and Ca2+ increased the activity of the recombinant α-amylase whereas the enzyme was inhibited by Cu2+, Zn2+, Hg2+, Pb2+, Fe3+ and Mn2+. Thin layer chromatography results confirmed that monosaccharide, disaccharide and maltotriose are the hydrolysis products. The results of our study suggest that this enzyme has considerable potential in industrial applications.
Flowable Bulk-Fill Materials Compared to Nano Ceramic Composites for Class I Cavities Restorations in Primary Molars: A Two-Year Prospective Case-Control Study

Background: The aim of this split-mouth study is to compare the results of 24 months’ clinical performance of primary molar Class I restorations with a nano-ceramic composite, Ceram•X mono (Dentsply) with a flowable bulk-fill material regular viscosity, SDR (Dentsply). Methods: Following the ethical approval, 27 patients with at least two class I cavities in primary molars were included in the study. A total number of 54 restorations were conducted (n = 27 for Ceram X and n = 27 for SDR). Restorations were evaluated at baseline, 6, 18, and 24 months, according to the modified Ryge criteria. The cavosurface marginal discoloration and color match were evaluated visually after air-drying the tooth and after removing the plaque (if necessary). Results: At 24 months’ follow-up, 54 restorations showed similar clinical performance. The statistical analysis did not reveal any statistical significance in the values between the groups in 7 out of 7 modified Ryge criteria. However, two restorations in both groups received Bravo ratings in the cavosurface marginal discoloration scoring. No side effects were reported by the participants of the study. Conclusion: Restorations with both materials (Ceram•X mono and SDR) have provided almost identical results.
Differential Gene Expression in Articular Cartilage and Subchondral Bone of Neonatal and Adult Horses

Skeletogenesis is complex and incompletely understood. Derangement of this process likely underlies developmental skeletal pathologies. Examination of tissue-specific gene expression may help elucidate novel skeletal developmental pathways that could contribute to disease risk. Our aim was to identify and functionally annotate differentially expressed genes in equine neonatal and adult articular cartilage (AC) and subchondral bone (SCB). RNA was sequenced from healthy AC and SCB from the fetlock, hock, and stifle joints of 6 foals (≤4 weeks of age) and six adults (8–12 years of age). There was distinct clustering by age and tissue type. After differential expression analysis, functional annotation and pathway analysis were performed using PANTHER and Reactome. Approximately 1115 and 3574 genes were differentially expressed between age groups in AC and SCB, respectively, falling within dozens of overrepresented gene ontology terms and enriched pathways reflecting a state of growth, high metabolic activity, and tissue turnover in the foals. Enriched pathways were dominated by those related to extracellular matrix organization and turnover, and cell cycle and signal transduction. Additionally, we identified enriched pathways related to neural development and neurotransmission in AC and innate immunity in SCB. These represent novel potential mechanisms for disease that can be explored in future work.
Limited evidence for spatial resource partitioning across temperate grassland biodiversity experiments.

Locally, plant species richness supports many ecosystem functions. Yet, the mechanisms driving these often-positive biodiversity-ecosystem functioning relationships are not well understood. Spatial resource partitioning across vertical resource gradients is one of the main hypothesized causes for enhanced ecosystem functioning in more biodiverse grasslands. Spatial resource partitioning occurs if species differ in where they acquire resources and can happen both above- and belowground. However, studies investigating spatial resource partitioning in grasslands provide inconsistent evidence. We present the results of a meta-analysis of 21 data sets from experimental species-richness gradients in grasslands. We test the hypothesis that increasing spatial resource partitioning along vertical resource gradients enhances ecosystem functioning in diverse grassland plant communities above- and belowground. To test this hypothesis, we asked three questions: 1. Does species richness enhance biomass production or community resource uptake across sites? 2. Is there evidence of spatial resource partitioning as indicated by resource tracer uptake and biomass allocation above- and belowground? 3. Is evidence of spatial resource partitioning correlated with increased biomass production or community resource uptake? Although plant species richness enhanced community nitrogen and potassium uptake and biomass production above- and belowground, we found that plant communities did not meet our criteria for spatial resource partitioning, though they did invest in significantly more aboveground biomass in higher canopy layers in mixture relative to monoculture. Furthermore, the extent of spatial resource partitioning across studies was not positively correlated with either biomass production or community resource uptake. Our results suggest that spatial resource partitioning across vertical resource gradients alone does not offer a general explanation for enhanced ecosystem functioning in more diverse temperate grasslands.
New Recommendations on the Use of R-Squared Differences in Multilevel Model Comparisons

Abstract When comparing multilevel models (MLMs) differing in fixed and/or random effects, researchers have had continuing interest in using R-squared differences to communicate effect size and importance of included terms. However, there has been longstanding confusion regarding which R-squared difference measures should be used for which kind of MLM comparisons. Furthermore, several limitations of recent studies on R-squared differences in MLM have led to misleading or incomplete recommendations for practice. These limitations include computing measures that are by definition incapable of detecting a particular type of added term, considering only a subset of the broader class of available R-squared difference measures, and incorrectly defining what a given R-squared difference measure quantifies. The purpose of this paper is to elucidate and resolve these issues. To do so, we define a more general set of total, within-cluster, and between-cluster R-squared difference measures than previously considered in MLM comparisons and give researchers concrete step-by-step procedures for identifying which measure is relevant to which model comparison. We supply simulated and analytic demonstrations of limitations of previous MLM studies on R-squared differences and show how application of our step-by-step procedures and general set of measures overcomes each. Additionally, we provide and illustrate graphical tools and software allowing researchers to automatically compute and visualize our set of measures in an integrated manner. We conclude with recommendations, as well as extensions involving (a) how our framework relates to and can be used to obtain pseudo-R-squareds, and (b) how our framework can accommodate both simultaneous and hierarchical model-building approaches.
The technical and economic impact of veterinary interventions aimed at reducing antimicrobial use on broiler farms

Antimicrobial resistance is a global threat for both human and animal health. One of the main drivers of antimicrobial resistance is inappropriate antimicrobial use in livestock production. The aim of this study was to examine the technical and economic impact of tailor-made interventions, aimed at reducing antimicrobial use in broiler production. Historical (i.e., before intervention) and observational (i.e., after intervention) data were collected at 20 broiler farms. Results indicate that average daily gain and mortality generally increased after intervention, whereas feed conversion and antimicrobial use decreased. Economic performance after interventions was generally higher than before the interventions. Sensitivity analyses on price changes confirm the robustness of the findings.
A Transcriptionally Definable Subgroup of Triple-Negative Breast and Ovarian Cancer Samples Shows Sensitivity to HSP90 Inhibition

Purpose: We hypothesized that integrated analysis of cancer types from different lineages would reveal novel molecularly defined subgroups with unique therapeutic vulnerabilities. On the basis of the molecular similarities between subgroups of breast and ovarian cancers, we analyzed these cancers as a single cohort to test our hypothesis. Experimental Design: Identification of transcriptional subgroups of cancers and drug sensitivity analyses were performed using mined data. Cell line sensitivity to Hsp90 inhibitors (Hsp90i) was tested in vitro. The ability of a transcriptional signature to predict Hsp90i sensitivity was validated using cell lines, and cell line- and patient-derived xenograft (PDX) models. Mechanisms of Hsp90i sensitivity were uncovered using immunoblot and RNAi. Results: Transcriptomic analyses of breast and ovarian cancer cell lines uncovered two mixed subgroups comprised primarily of triple-negative breast and multiple ovarian cancer subtypes. Drug sensitivity analyses revealed that cells of one mixed subgroup are significantly more sensitive to Hsp90i compared with cells from all other cancer lineages evaluated. A gene expression classifier was generated that predicted Hsp90i sensitivity in vitro, and in cell line- and PDXs. Cells from the Hsp90i-sensitive subgroup underwent apoptosis mediated by Hsp90i-induced upregulation of the proapoptotic proteins Bim and PUMA. Conclusions: Our findings identify Hsp90i as a potential therapeutic strategy for a transcriptionally defined subgroup of ovarian and breast cancers. This study demonstrates that gene expression profiles may be useful to identify therapeutic vulnerabilities in tumor types with limited targetable genetic alterations, and to identify molecularly definable cancer subgroups that transcend lineage.
Multidrug-Resistant Escherichia coli, Klebsiella pneumoniae and Staphylococcus spp. in Houseflies and Blowflies from Farms and Their Environmental Settings

Background: Antimicrobial resistance is rising globally at an alarming rate. While multiple active surveillance programs have been established to monitor the antimicrobial resistance, studies on the environmental link to antimicrobial spread are lacking. Methods: A total of 493 flies were trapped from a dairy unit, a dog kennel, a poultry farm, a beef cattle unit, an urban trash facility and an urban downtown area to isolate Escherichia coli, Klebsiella pneumoniae and Staphylococcus spp. for antimicrobial susceptibility testing and molecular characterization. Results: E. coli, K. pneumoniae and coagulase-negative Staphylococcus were recovered from 43.9%, 15.5% and 66.2% of the houseflies, and 26.0%, 19.2%, 37.0% of the blowflies, respectively. In total, 35.3% of flies were found to harbor antimicrobial-resistant bacteria and 9.0% contained multidrug-resistant isolates. Three Staphylococcus aureus isolates were recovered from blowflies while three extended spectrum beta lactamase (ESBL)-carrying E. coli and one ESBL-carrying K. pneumoniae were isolated from houseflies. Whole genome sequencing identified the antimicrobial resistance genes blaCMY-2 and blaCTXM-1 as ESBLs. Conclusion: Taken together, our data indicate that flies can be used as indicators for environmental contamination of antimicrobial resistance. More extensive studies are warranted to explore the sentinel role of flies for antimicrobial resistance.
Oral arsenic trioxide ORH-2014 pharmacokinetic and safety profile in patients with advanced hematologic disorders

Daily intravenous arsenic trioxide administered with all-trans retinoid acid, the standard-of-care for acute promyelocytic leukemia, is costly and challenging to administer. ORH-2014 is a novel, oral arsenic trioxide formulation, consisting of micron-size drug particles with rapid dissolution and high bioavailability. We conducted a multicenter phase 1 dose-escalating study in patients with advanced hematologic malignancies. Twelve patients received ORH-2014 at 5 mg (n=3), 10 mg (n=6), or 15 mg (n=3) orally once a day (fasted state). Objectives were to assess the safety, tolerability and pharmacokinetics of ORH-2014 to support a dose recommendation for future trials. The median age of the patients was 77 years (range: 45-81) and they had received a median of two (range: 1-5) prior therapies. There were no dose limiting toxicities and no drug-related severe adverse events, except one grade III QT prolongation occurring beyond the dose limiting toxicity assessment period and resolving after treatment interruption. ORH-2014 steady-state plasma concentration was reached on day 15. ORH-2014, 15 mg Cmax was comparable to the calculated approved dose of intravenous arsenic trioxide (mean [% coefficient of variation]: 114 [21%] vs. 124 [60%] ng/mL) and area under the curve from 0 to 24 hours was 2,140 (36%) versus 1,302 (30%) h*ng/mL. These results indicate that ORH-2014 at 15 mg is safe, bioavailable, and provides the required arsenic exposure compared to intravenous arsenic trioxide at the approved dose (0.15 mg/kg); this ORH-2014 dose is recommended for future trials. (NCT03048344; www.clin-icaltrials.gov).
Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double‐blind, placebo‐controlled, multicenter trial: The MASTERS trial

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double‐blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p < .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p = .007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228.