Miracle-dz/UniFAR-FTUs huggingface dataset:
Ethanol Decreases Pseudomonas aeruginosa Flagellar Motility through the Regulation of Flagellar Stators

Ethanol is an important biologically active molecule produced by many bacteria and fungi. It has also been identified as a potential marker for disease state in cystic fibrosis. In line with previous data showing that ethanol promotes biofilm formation by Pseudomonas aeruginosa, here we report that ethanol reduces swimming motility using some of the same proteins involved in surface sensing. We propose that these data may provide insight into how microbes, via their metabolic byproducts, can influence P. aeruginosa colocalization in the context of infection and in other polymicrobial settings. ABSTRACT Pseudomonas aeruginosa frequently encounters microbes that produce ethanol. Low concentrations of ethanol reduced P. aeruginosa swim zone area by up to 45% in soft agar. The reduction of swimming by ethanol required the flagellar motor proteins MotAB and two PilZ domain proteins (FlgZ and PilZ). PilY1 and the type 4 pilus alignment complex (comprising PilMNOP) were previously implicated in MotAB regulation in surface-associated cells and were required for ethanol-dependent motility repression. As FlgZ requires the second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) to represses motility, we screened mutants lacking genes involved in c-di-GMP metabolism and found that mutants lacking diguanylate cyclases SadC and GcbA were less responsive to ethanol. The double mutant was resistant to its effects. As published previously, ethanol also represses swarming motility, and the same genes required for ethanol effects on swimming motility were required for its regulation of swarming. Microscopic analysis of single cells in soft agar revealed that ethanol effects on swim zone area correlated with ethanol effects on the portion of cells that paused or stopped during the time interval analyzed. Ethanol increased c-di-GMP in planktonic wild-type cells but not in ΔmotAB or ΔsadC ΔgcbA mutants, suggesting c-di-GMP plays a role in the response to ethanol in planktonic cells. We propose that ethanol produced by other microbes induces a regulated decrease in P. aeruginosa motility, thereby promoting P. aeruginosa colocalization with ethanol-producing microbes. Furthermore, some of the same factors involved in the response to surface contact are involved in the response to ethanol. IMPORTANCE Ethanol is an important biologically active molecule produced by many bacteria and fungi. It has also been identified as a potential marker for disease state in cystic fibrosis. In line with previous data showing that ethanol promotes biofilm formation by Pseudomonas aeruginosa, here we report that ethanol reduces swimming motility using some of the same proteins involved in surface sensing. We propose that these data may provide insight into how microbes, via their metabolic byproducts, can influence P. aeruginosa colocalization in the context of infection and in other polymicrobial settings.
The antipsychotic amisulpride: ultrastructural evidence of its secretory activity in salivary glands.

OBJECTIVE Amisulpride is reported to inhibit clozapine-induced sialorrhea. Preclinically, clozapine evokes muscarinic-M1-type-mediated secretion that, however, amisulpride does not reduce. Instead, amisulpride, without causing any overt secretion per se, enhances both nerve- and autonomimetic-evoked salivation by unknown mechanism(s). Hypothesizing that amisulpride prepares the gland for secretion, we looked for ultrastructural events indicating secretory activity in intercellular canaliculi of serous/seromucous cells, that is, density increase in protrusions (reflecting anchored granules) and in microbuds (reflecting recycling membranes and/or vesicle secretion) and decrease in microvilli (reflecting the cytoskeletal re-arrangement related to exocytosis). MATERIAL AND METHODS Rat parotid and submandibular glands were exposed to amisulpride in vivo or in vitro. Glands were processed for transmission electron and scanning electron microscopy and then morphometrically assessed. RESULTS Cells were packed with secretory granules. The density of protrusions increased in both glands, whereas significant and parallel changes in microvilli and microbuds occurred only in parotid glands, and in vitro. CONCLUSIONS Amisulpride induced ultrastructural signs of secretory activity but to varying extent; in submandibular glands, in contrast to parotid glands, changes were not brought beyond the granular anchoring stage. Amisulpride may provide an overall readiness for secretion that will result in augmented responses to agonists, a phenomenon of potential interest in dry-mouth treatment.
Accuracy of multi-implant impressions using 3D-printing custom trays and splinting versus conventional techniques for complete arches.

PURPOSE To assess the three-dimensional (3D) accuracy of multi-implant impressions for complete arches obtained using 3D printing technology, and to determine the clinical feasibility of this approach by comparing the results obtained with those obtained with conventional impression techniques. MATERIALS AND METHODS A maxillary model matrix with four implant analogs was used to fabricate 10 stone reference models (control) to simulate edentulous patients. Ten 3D-printed impressions were made using polylactic acid custom open trays with component splinting (3D-printed group). To make 10 conventional impressions of the reference models, the poly(methyl methacrylate) open trays with splinting technique was used (conventional group). Impressions were poured with a type IV dental stone, which had been digitalized utilizing a high-resolution laboratory scanner after connecting the polymer scan bodies. Standard tessellation language (STL) datasets from the two groups of stone models were superimposed with the corresponding reference models. The interimplant distances and interimplant angulations for each implant pair were measured for the reference models and for the two test groups' definitive models, to assess 3D deviations. In addition, the mechanical properties of polylactic acid and poly(methyl methacrylate) tray materials were compared by means of three-point loading and tensile bond tests. The Student t test was used to compare the differences in implant position and mechanical properties between the two groups, while implant angulations were analyzed with Wilcoxon's rank-sum test, at P = . 05. RESULTS There was less implant-position deviation for the 3D-printed group (mean ± SD: 56.37 ± 12.52 μm) than for the conventional group (71.94 ± 18.86 μm) (P = .014). No significant differences were found in angular deviation between the two groups (P > .05). Flexural strength results suggested that polylactic acid (112.7 ± 1.62 MPa) was stronger than poly(methyl methacrylate) (104.0 ± 2.17 MPa; P < .0001). The tensile bond strength of polylactic acid (0.07 ± 0.005 MPa) was higher than that of poly(methyl methacrylate) (0.03 ± 0.004 MPa; P < .0001). CONCLUSION The 3D-printing multi-implant impression technique could be an alternative to conventional impression techniques for complete arches.
Dietary Flavonoids as Cancer Chemopreventive Agents: An Updated Review of Human Studies

Over the past few years, interest in health research has increased, making improved health a global goal for 2030. The purpose of such research is to ensure healthy lives and promote wellbeing across individuals of all ages. It has been shown that nutrition plays a key role in the prevention of some chronic diseases such as obesity, cardiovascular disease, diabetes, and cancer. One of the aspects that characterises a healthy diet is a high intake of vegetables and fruits, as both are flavonoid-rich foods. Flavonoids are one of the main subclasses of dietary polyphenols and possess strong antioxidant activity and anti-carcinogenic properties. Moreover, some population-based studies have described a relationship between cancer risk and dietary flavonoid intake. In this context, the goal of this review was to provide an updated evaluation of the association between the risk of different types of cancers and dietary flavonoid intake. We analysed all relevant epidemiological studies from January 2008 to March 2019 using the PUBMED and Web of Science databases. In summary, this review concludes that dietary flavonoid intake is associated with a reduced risk of different types of cancer, such as gastric, breast, prostate, and colorectal cancers.
Induction of β-adrenergic metaplasticity of LTP requires intact anchoring of PKA

Beta-adrenergic receptors (β-ARs) prime hippocampal synapses to stabilize long-term potentiation (LTP). This “metaplasticity” can persist for 1–2 h after pharmacologic activation of β-ARs. It requires activation of PKA (cAMP-dependent protein kinase) during β-AR priming. A-kinase anchoring proteins (AKAPs) tether PKA to downstream signaling proteins. We hypothesized that induction of this metaplasticity requires intact functioning of AKAPs. Acute application of stearated ht31, a membrane-permeant inhibitor of AKAPs, either during β-AR activation 30 min prior to LTP induction or during LTP induction, attenuated the persistence of LTP. A control, inactive ht31 peptide did not affect β-AR-mediated metaplasticity. These findings implicate PKA anchoring in the induction of β-adrenergic metaplasticity of LTP.
Effect of Graphene Oxide Synthesis Method on Properties and Performance of Polysulfone-Graphene Oxide Mixed Matrix Membranes

Graphene oxide (GO) has shown great promise as a nanofiller to enhance the performance of mixed matrix composite membranes (MMMs) for water treatment applications. However, GO can be prepared by various synthesis routes, leading to different concentrations of the attached oxygen functional groups. In this research, GO produced by the Hummers’, Tour, and Staudenmaier methods were characterized and embedded at various fractions into the matrix of polysulfone (PSf) and used to prepare microfiltration membranes via the phase inversion process. The effects of the GO preparation method and loading on the membrane characteristics, as well as performance for oil removal from an oil-water emulsion, are analyzed. Our results reveal that GO prepared by the Staudenmaier method has a higher concentration of the more polar carbonyl group, increasing the membrane hydrophilicity and porosity compared to GO prepared by the Hummers’ and Tour methods. On the other hand, the Hummers’ and Tour methods produce GO with larger sheet size, and are more effective in enhancing the mechanical properties of the PSf membrane. Finally, all MMMs exhibited improved water flux (up to 2.7 times) and oil rejection, than those for the control PSf sample, with the optimum GO loading ranged between 0.1–0.2 wt%.
Chemical Composition, Antioxidant, and Antimicrobial Activities of Vetiveria zizanioides (L.) Nash Essential Oil Extracted by Carbon Dioxide Expanded Ethanol

In the present study, the composition of essential oil isolated from the roots of Vetiveria zizanioides (L.) Nash, harvested in China, was studied, along with the bioactivities. A green novel method using an eco-friendly solvent, CO2-pressurized ethanol, or carbon dioxide expanded ethanol (CXE) was employed to isolate the essential oil from the root of Vetiveria zizanioides (L.) Nash with the purpose of replacing the traditional method and supercritical fluid extraction (SFE). After investigating the major operating factors of CXE, the optimal conditions were obtained as follows: 8.4 MPa, 50 °C, 5 mL/min ethanol, and 0.22 mole fraction of CO2, presenting an extraction oil that ranged from 5.12% to 7.42%, higher than that of hydrodistillation (HD) or indirect vapor distillation (IVD). The Gas Chromatography-Mass Spectrometry (GC-MS) analysis showed that three major components, including valerenol (18.48%), valerenal (10.21%), and β-Cadinene (6.23%), are found in CXE oil, while a total of 23 components were identified, 48 components less than using conventional hydrodistillation. Furthermore, the antimicrobial activities of root oils were evaluated by the microdilution method, which showed that CXE oil exhibited an ability against Gram-positive bacteria, especially Staphylococcus aureus, approximately equivalent to traditional samples. Additionally, the DPPH free radical scavenging assay demonstrated that the antioxidant abilities of root oils were sorted in the descending order: IVD > HD > CXE > SFE. In conclusion, after a comprehensive comparison with the conventional methods, the CXE-related technique might be a promising green manufacturing pattern for the production of quality vetiver oil, due to the modification of ethanol by the variable addition of non-polar compressible CO2, ultimately resulting in a prominent dissolving capability for the extraction of vetiver solutes.
Mechanistic Insights into the Antimicrobial Actions of Metallic Nanoparticles and Their Implications for Multidrug Resistance

Multiple drug-resistant bacteria are a severe and growing public health concern. Because relatively few antibiotics have been approved over recent years and because of the inability of existing antibiotics to combat bacterial infections fully, demand for unconventional biocides is intense. Metallic nanoparticles (NPs) offer a novel potential means of fighting bacteria. Although metallic NPs exert their effects through membrane protein damage, superoxide radicals and the generation of ions that interfere with the cell granules leading to the formation of condensed particles, their antimicrobial potential, and mechanisms of action are still debated. This article discusses the action of metallic NPs as antibacterial agents, their mechanism of action, and their effect on bacterial drug resistance. Based on encouraging data about the antibacterial effects of NP/antibiotic combinations, we propose that this concept be thoroughly researched to identify means of combating drug-resistant bacteria.
Collective Efficacy as a Mediator of the Trustworthiness – Performance Relationship in Computer-Mediated Team-based Contexts

Abstract The current study investigated the role of trustworthiness perceptions at the individual level and collective efficacy at the team level on team performance in computer-mediated teams using multi-level structural equation modeling (MSEM). It was hypothesized that trustworthiness perceptions and collective efficacy would predict team performance, and collective efficacy would partially mediate the trustworthiness – performance relationship in computer-mediated teams. Sixty-four teams (five participants each) engaged in a computer-mediated task across two experimental sessions. Trustworthiness measured after session 1, collective efficacy measured after sessions 1 and 2, and team performance measured of sessions 1 and 2 were used to build the MSEM. The half longitudinal model for assessing mediation was used to examine the influence of trustworthiness perceptions on performance through collective efficacy over time. Results demonstrated support for the hypothesized model, such that trustworthiness perceptions demonstrated indirect effects on performance through collective efficacy. These findings extend past research by identifying an emergent mechanism by which trustworthiness is important for team performance in computer-mediated teams.
Crystal structure of the heterodimeric complex of LXRα and RXRβ ligand‐binding domains in a fully agonistic conformation

The nuclear receptor heterodimers of liver X receptor (LXR) and retinoid X receptor (RXR) are key transcriptional regulators of genes involved in lipid homeostasis and inflammation. We report the crystal structure of the ligand‐binding domains (LBDs) of LXRα and RXRβ complexed to the synthetic LXR agonist T‐0901317 and the RXR agonist methoprene acid (Protein Data Base entry 1UHL). Both LBDs are in agonist conformation with GRIP‐1 peptides bound at the coactivator binding sites. T‐0901317 occupies the center of the LXR ligand‐binding pocket and its hydroxyl head group interacts with H421 and W443, residues identified by mutational analysis as critical for ligand‐induced transcriptional activation by T‐0901317 and various endogenous oxysterols. The topography of the pocket suggests a common anchoring of these oxysterols via their 22‐, 24‐ or 27‐hydroxyl group to H421 and W443. Polyunsaturated fatty acids act as LXR antagonists and an E267A mutation was found to enhance their transcriptional inhibition. The present structure provides a powerful tool for the design of novel modulators that can be used to characterize further the physiological functions of the LXR–RXR heterodimer.
Seeing the forest through the trees: comprehensive inference on individual mating patterns in a mixed stand of Quercus robur and Q. petraea.

BACKGROUND AND AIMS Sexual reproduction is one of the most important moments in a life cycle, determining the genetic composition of individual offspring. Controlled pollination experiments often show high variation in the mating system at the individual level, suggesting a persistence of individual variation in natural populations. Individual variation in mating patterns may have significant adaptive implications for a population and for the entire species. Nevertheless, field data rarely address individual differences in mating patterns, focusing rather on averages. This study aimed to quantify individual variation in the different components of mating patterns. METHODS Microsatellite data were used from 421 adult trees and 1911 seeds, structured in 72 half-sib families collected in a single mixed stand of Quercus robur and Q. petraea in northern Poland. Using a Bayesian approach, mating patterns were investigated, taking into account pollen dispersal, male fecundity, possible hybridization and heterogeneity in immigrant pollen pools. KEY RESULTS Pollen dispersal followed a heavy-tailed distribution (283 m on average). In spite of high pollen mobility, immigrant pollen pools showed strong genetic structuring among mothers. At the individual level, immigrant pollen pools showed highly variable divergence rates, revealing that sources of immigrant pollen can vary greatly among particular trees. Within the stand, the distribution of male fecundity appeared highly skewed, with a small number of dominant males, resulting in a ratio of census to effective density of pollen donors of 5·3. Male fecundity was not correlated with tree diameter but showed strong cline-like spatial variation. This pattern can be attributed to environmental variation. Quercus petraea revealed a greater preference (74 %) towards intraspecific mating than Q. robur (36 %), although mating preferences varied among trees. CONCLUSIONS Mating patterns can reveal great variation among individuals, even within a single even-age stand. The results show that trees can mate assortatively, with little respect for spatial proximity. Such selective mating may be a result of variable combining compatibility among trees due to genetic and/or environmental factors.
Cerebellar Stellate Cell Excitability Is Coordinated by Shifts in the Gating Behavior of Voltage-Gated Na+ and A-Type K+ Channels

Abstract Neuronal excitability in the vertebrate brain is governed by the coordinated activity of both ligand- and voltage-gated ion channels. In the cerebellum, spontaneous action potential (AP) firing of inhibitory stellate cells (SCs) is variable, typically operating within the 5- to 30-Hz frequency range. AP frequency is shaped by the activity of somatodendritic A-type K+ channels and the inhibitory effect of GABAergic transmission. An added complication, however, is that whole-cell recording from SCs induces a time-dependent and sustained increase in membrane excitability making it difficult to define the full range of firing rates. Here, we show that whole-cell recording in cerebellar SCs of both male and female mice augments firing rates by reducing the membrane potential at which APs are initiated. AP threshold is lowered due to a hyperpolarizing shift in the gating behavior of voltage-gated Na+ channels. Whole-cell recording also elicits a hyperpolarizing shift in the gating behavior of A-type K+ channels which contributes to increased firing rates. Hodgkin–Huxley modeling and pharmacological experiments reveal that gating shifts in A-type K+ channel activity do not impact AP threshold, but rather promote channel inactivation which removes restraint on the upper limit of firing rates. Taken together, our work reveals an unappreciated impact of voltage-gated Na+ channels that work in coordination with A-type K+ channels to regulate the firing frequency of cerebellar SCs.
Bilateral postoperative ultrasound-guided erector spinae plane block in open abdominal hysterectomy: a case series and cadaveric investigation

Abstract We anticipated that bilateral Erector spinae plane (ESP) block, which was applied in 10 patients starting from lower thoracic levels (T9) might provide effective postoperative analgesia in open abdominal hysterectomies. In addition, we aimed to obtain anatomic observation of the local anaesthetic (LA) spread in the ESP block by injecting methylene blue on 4 cadavers. All the patients had excellent pain relief. There was an extensive spread to the erector spinae muscle (ESM) involving several segmental levels on cadavers. We observed the spread of dye on the ventral and dorsal rami in the paravertebral space and as an additional finding, the dye had extended to the canal vertebralis. There was a spread of dye on the dura mater. ESP block can be used with new indications and it is an effective technique for major abdominal surgery when is applied to the lower vertebral levels. Randomized controlled trials are required to explore the clinical implications of our findings.
The Single‐Dose Pharmacokinetics of Midazolam and Its Primary Metabolite in Pediatric Patients after Oral and Intravenous Administration

The first‐dose pharmacokinetics of midazolam and its primary α‐hydroxy metabolite were studied after single‐dose administration. Eligible study patients were enrolled into one of three study arms: Arm I (midazolam/metabolite pharmacokinetic evaluation after oral administration of a syrup formulation), Arm II (the absolute bioavailability of midazolam syrup), and Arm III (midazolam and metabolite pharmacokinetics after IV administration). Complete blood sampling for pharmacokinetic analysis was available in 87 subjects. Midazolam absorption after administration of the oral syrup formulation was rapid, with adolescents absorbing the drug at approximately half the rate observed in younger children (ages 2 to < 12 years). Furthermore, midazolam t1/2 was prolonged and CL/F reduced in adolescents as compared with younger children. Although the midazolam Vd/F appeared larger in the youngest age group after oral administration, this observation was not apparent after IV dosing, suggesting subject differences in bioavailability rather than distribution. Like midazolam, the disposition characteristics for α‐hydroxymidazolam were also highly variable, with the greatest formation of metabolite (reflected by the AUC ratio) observed in children ages 2 to < 12 years. The AUC ratios of α‐hydroxymidazolam to midazolam after IV dosing were similar across all age groups and were smaller than corresponding values following oral administration. The absolute bioavailability of midazolam averaged 36% with a very broad range (9%‐71%). No relationship between midazolam bioavailability and age was observed. Overall, the disposition characteristics of midazolam and its α‐hydroxy metabolite were highly variable, appeared independent of age and dose administered, and were linear over the dose range studied (0.25 to 1 mg/kg). These data suggest that an initial oral dose of 0.2 to 0.3 mg/kg should be adequate for successful sedation of most pediatric patients. The inherent variability in midazolam bioavailability and metabolism underscores the importance of titrating midazolam dose to desired effect.