Miracle-dz/UniFAR-FTUs huggingface dataset:
The APC/CTE E3 Ubiquitin Ligase Complex Mediates the Antagonistic Regulation of Root Growth and Tillering by ABA and GA

Abscisic acid and gibberellic acid exert opposite effects on root growth and tillering by antagonistically regulating the APC/CTE-mediated degradation of rice SHORT-ROOT1 (OsSHR1) and MONOCULM1 (MOC1). The antagonistic regulation of seed germination by the phytohormones abscisic acid (ABA) and gibberellic acid (GA) has been well-established. However, how these phytohormones antagonistically regulate root growth and branching (tillering in rice, Oryza sativa) remains obscure. Rice TILLER ENHANCER (TE) encodes an activator of the APC/CTE E3 ubiquitin ligase complex that represses tillering but promotes seed germination. In this study, we identified a dual role of GA and APC/CTE in regulating root growth. High GA levels can activate APC/CTE to promote the degradation of rice SHORT-ROOT1 (OsSHR1, a key factor promoting root growth) in the root meristem (RM) or MONOCULM1 (MOC1, a key factor promoting tillering) in the axillary meristem (AM), leading to restricted root growth and tillering, while low GA levels can activate the role of APC/CTE in stimulating RM cell division to promote root growth. In addition, moderate enhancement of ABA signaling helps maintain the RM and AM size, sustaining root growth and tillering by antagonizing the GA-promoted degradation of OsSHR1 and MOC1 through the SnRK2-APC/CTE regulatory module. We conclude that APC/CTE plays a key role in regulating plant architecture by mediating the crosstalk between ABA and GA signaling pathways.
Catheter Access Port (Computed Tomography) Myelography in Intrathecal Drug Delivery Troubleshooting: A Case Series of 70 Procedures

Intrathecal drug delivery is used for the treatment of intractable spasticity, dystonia, and pain. When the symptomatology fails to respond to therapy, the cause could be failure of the medication infusion. The purpose of this study is to assess pump catheter access port (CAP)‐myelography and CAP‐CT‐myelography as advanced imaging methods in treatment failure.
Solanum leaves extracts exhibit antioxidant properties and inhibit monoamine oxidase and acetylcholinesterase activities (in vitro) in Drosophila melanogaster

Abstract Background This study sought to determine the in vitro antioxidant, anti-monoamine oxidase and anticholinesterase properties of extracts (aqueous and alkaloid) of two tropical vegetables from Solanum spp- African eggplant (Solanum macrocarpon L) and black nightshade (Solanum nigrum L) as indices of their neuroprotective properties. Methods Both aqueous and alkaloid extracts of African eggplant (AE) and black nightshade (BN) were prepared by solvent extraction according to standard methods. Thereafter, the inhibitory effects of the extracts on monoamine oxidase (MAO) and acetylcholinesterase (AChE) activities, as well as their free radical-scavenging and reducing abilities were assessed. Also, phytochemical analysis for phenols, flavonoids, and alkaloids were carried out. Results The results showed that the extracts inhibited MAO and AChE activities dose dependently, with aqueous extracts showing significantly higher MAO inhibition that the alkaloid extracts from both samples, but in all, BN showed higher MAO inhibitory effect compared to AE; the reverse was however, observed for AChE inhibition. Furthermore, the aqueous extracts showed significantly higher antioxidant properties than the alkaloid extracts, while BN had higher antioxidant properties compared to AN. The phytochemical analysis also showed that BN had significantly higher amount of phenols, flavonoids, and alkaloids than AE. Conclusions The anti-monoamine oxidase, anticholinesterase, and antioxidant properties exhibited by extracts from both samples could contribute to their neuroprotective abilities. Thus, these vegetables can be potential sources of functional foods and nutraceuticals in the management of neurodegenerative diseases, especially in the tropics.
The Association of Perfluoroalkyl Substances Exposure and Metabolic Syndrome in U.S. Adults

Background: Perfluoroalkyl substances (PFASs) are persistent synthetic compounds that have been environmental contaminants since the 1950s. Exposure in the general population can be through food and water ingestion, use of non-stick cookware, and dust from stain-resistant carpet. Studies have suggested PFASs act as endocrine disrupters and to affect liver and immune function, as well as cause increases in serum lipid levels. Objective: To explore the association between six common detectable PFASs and the metabolic syndrome (MetS) in United States (U.S.) adults. Methods: Data from 739 participants aged 20 years and older from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed. Descriptive analysis was performed on the dataset. Univariate and multivariable logistic regression analysis was used to determine independent association between the serum PFASs and MetS controlling for confounders including age, ethnicity, income, smoking status, and gender. Results: In the descriptive analysis, the overall prevalence of MetS in the sample population (49.5%) was higher than previously reported in the literature for U.S. adults, but distribution remained relatively equal between males (48.9%) and females (50.1%). In unadjusted logistic regression analysis, each of the six PFASs showed a positive association with MetS, but only PFOS-branched (p < .001) and PFHxS (p = .019) were statistically significant. However, after controlling for confounders, no significant association between the presence of PFASs and MetS
Efficacy and safety of microwave ablation treatment for secondary hyperparathyroidism: systematic review and meta-analysis

Abstract Purpose The present systematic review and meta-analysis was designed to evaluate the efficacy and safety of microwave ablation (MWA) treatment for secondary hyperparathyroidism (SHPT). Materials and methods The study authors systematically searched the Web of Science, Cochrane Library, PubMed, Embase and Ovid databases for studies published in English prior to 7October 2019. All studies included in the meta-analysis measured levels of parathyroid hormone (PTH), calcium and phosphorus, and included data related to complications following MWA treatment for SHPT. Results The meta-analysis ultimately included 233 patients from two retrospective cohort studies and six retrospective self-control studies. Compared to PTH level measurements obtained after MWA, measurements obtained at one day (weighted mean differences (WMD): 890.314, 95% confidence interval (CI): 767.121–1013.506, p < 0.01) , one week (WMD: 860.298, 95% CI: 759.401–961.194, p < 0.01), one month (WMD: 800.846, 95% CI: 687.709–913.983, p < 0.01) and six months (WMD: 860.847, 95% CI: 745.214–976.480, p < 0.01) after MWA were significantly lower. Calcium and phosphorus levels at one day and one week after MWA were also significantly lower than those measured before MWA. After MWA, the incidence of nerve injury was 1.2% (3/233; effect size (ES): 0.022, 95% CI: −0.003–0.048, p < 0.01). After MWA, the incidence of hypocalcemia was 15.8% (37/233; ES: 0.449, 95% CI: 0.341–0.556, p < 0.01). Conclusion The preliminary results of this meta-analysis indicate that MWA may be effective and safe in treating patients with SHPT, and that future prospective research and randomized controlled trials (RCT) are necessary.
Novel Peptide from Commensal Staphylococcus simulans Blocks Methicillin-Resistant Staphylococcus aureus Quorum Sensing and Protects Host Skin from Damage

Recent studies highlight the abundance of commensal coagulase-negative staphylococci (CoNS) on healthy skin. Evidence suggests that CoNS actively shape the skin immunological and microbial milieu to resist colonization or infection by opportunistic pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), in a variety of mechanisms collectively termed colonization resistance. One potential colonization resistance mechanism is the application of quorum sensing, also called the accessory gene regulator (agr) system, which is ubiquitous among staphylococci. ABSTRACT Recent studies highlight the abundance of commensal coagulase-negative staphylococci (CoNS) on healthy skin. Evidence suggests that CoNS actively shape the skin immunological and microbial milieu to resist colonization or infection by opportunistic pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), in a variety of mechanisms collectively termed colonization resistance. One potential colonization resistance mechanism is the application of quorum sensing, also called the accessory gene regulator (agr) system, which is ubiquitous among staphylococci. Common and rare CoNS make autoinducing peptides (AIPs) that function as MRSA agr inhibitors, protecting the host from invasive infection. In a screen of CoNS spent media, we found that Staphylococcus simulans, a rare human skin colonizer and frequent livestock colonizer, released potent inhibitors of all classes of MRSA agr signaling. We identified three S. simulans agr classes and have shown intraspecies cross talk between noncognate S. simulans agr types for the first time. The S. simulans AIP-I structure was confirmed, and the novel AIP-II and AIP-III structures were solved via mass spectrometry. Synthetic S. simulans AIPs inhibited MRSA agr signaling with nanomolar potency. S. simulans in competition with MRSA reduced dermonecrotic and epicutaneous skin injury in murine models. The addition of synthetic AIP-I also effectively reduced MRSA dermonecrosis and epicutaneous skin injury in murine models. These results demonstrate potent anti-MRSA quorum sensing inhibition by a rare human skin commensal and suggest that cross talk between CoNS and MRSA may be important in maintaining healthy skin homeostasis and preventing MRSA skin damage during colonization or acute infection.
Periodontitis and risk for preeclampsia - a systematic review.

OBJECTIVES The aim of the study is to review systematic cohort and randomized trials on the relationship between periodontitis and preeclampsia. Periodontitis is an independent risk factor for preeclampsia (PE), and periodontal treatment could play a significant role in the prevention of this pregnancy complication. MATERIAL AND METHODS A total of 821 items (published until March 2019), thematically related to the relationship between periodontitis, its treatment and the incidence of preeclampsia, were collected from the databases of PubMed, Scopus, Google Scholar and the Polish Database of Medical Bibliography and analyzed. In the end, 6 cohort studies and 3 randomized controlled trials (from the years 2003-2016) were deemed eligible for the review. The main exclusion criteria were as follows: case-control and cross-sectional studies, medical and dental conditions. RESULTS A significant relationship between periodontitis and the risk for developing preeclampsia was demonstrated in 5 cohort trials, which was not confirmed by only 1 study. A total of 2724 pregnant women, including 195 (7.16%) with PE, were analyzed. In 3 randomized trials which assessed the impact of non-surgical treatment (scaling and root planing = SRP) on the occurrence of preeclampsia, the preventive effects of the implemented treatment was not confirmed. A total of 116 women from the group of 1825 pregnant subjects undergoing the non-surgical treatment (SRP) and 116 women from the control group of 1827 pregnant women were subsequently diagnosed with PE, which amounted to 6.30% and 6.35%, respectively. CONCLUSIONS The cohort studies indicated that periodontitis may result in an increased risk for developing PE. A more detailed analysis regarding the impact of potential risk factors and modification of further studies (clarification of how periodontitis and preeclampsia should be defined in observations, consideration of disease severity, earlier at 12-16 weeks of gestation - implementation of the non-surgical treatment, modification and extension of the classical protocol of the non-surgical treatment of periodontal diseases, as well as conducting European studies), are necessary due to considerable discrepancies in the available literature sources (cohort and randomized observations).
Uncharacteristic Task-Evoked Pupillary Responses Implicate Atypical Locus Ceruleus Activity in Autism

Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD. SIGNIFICANCE STATEMENT Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, including altered sensory responses and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus ceruleus (LC) activity, as the LC plays a critical role in attentional modulation. Specifically, LC activity is involved in regulating the trade-off between environmental exploration and focused attention. This study shows that, under tightly controlled conditions, task-evoked pupil responses, an LC activity proxy, are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.
Tumor Responsive and Tunable Polymeric Platform for Optimized Delivery of Paclitaxel to Treat Glioblastoma.

Current interstitial therapies for glioblastoma can overcome the blood-brain barrier, but fail to optimally release therapy at a rate which stalls cancer reoccurrence. To address this lapse, acetalated dextran (Ace-DEX) nanofibrous scaffolds were used for their unique degradation rates that translate to a broad range of drug release kinetics. A distinctive range of drug release rates was illustrated via electrospun Ace-DEX or poly(lactic acid) (PLA) scaffolds. Scaffold comprised of fast, medium, and slow degrading Ace-DEX resulted in 14.1, 2.9, and 1.3 percent paclitaxel released per day. To better understand the impact of paclitaxel release rate on interstitial therapy, two clinically relevant orthotopic glioblastoma mouse models were explored: 1) a surgical model of resection and recurrence (resection model) and 2) a distant metastasis model. The effect of unique drug release was illustrated in the resection model when a 78% long term survival was observed with combined fast and slow release scaffolds, in comparison to a survival of 20% when the same dose is delivered at a medium release rate. In contrast, only the fast release rate scaffold displayed treatment efficacy in the distant metastasis model. Additionally, the acid-sensitive Ace-DEX scaffolds were shown to respond to the lower pH conditions associated with GBM tumors, releasing more paclitaxel in vivo when a tumor was present in contrast to non-acid sensitive PLA scaffolds. The unique range of tunable degradation and stimuli-responsive nature makes Ace-DEX a promising drug delivery platform to improve interstitial therapy for glioblastoma.
In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain)

Abstract The N terminal domain (NTD) of Nucleocapsid protein (N protein) of coronavirus (CoV) binds to the viral (+) sense RNA and results in CoV ribonucleoprotien (CoV RNP) complex, essential for the virus replication. In this study, the RNA-binding N terminal domain (NTD) of the N protein was targeted for the identification of possible inhibitors of RNA binding. Two NTD structures of N proteins were selected (2OFZ and 1SSK, 92% homology) for virtual screening of 56,079 compounds from Asinex and Maybridge library to identify top 15 hits for each of the targets based on ‘docking score’. These top-hits were further screened for MM-GBSA binding free energy, pharmacokinetic properties (QikProp) and drug-likeness (SwissADME) and subjected to molecular dynamics (MD) studies. Two suitable binders (ZINC00003118440 and ZINC0000146942) against the target 2OFZ were identified. ZINC00003118440 is a theophylline derivative under the drug class ‘bronchodilators’ and further screening with approved bronchodilators was also studied to identify their ability to bind to the RNA binding region on the N protein. The other identified top hit is ZINC0000146942, which is a 3,4dihydropyrimidone class molecule. Hence this study suggests two important class of compounds, theophylline and pyrimidone derivaties as possible inhibitors of RNA binding to the N terminal domain of N protein of coronavirus, thus opening new avenues for in vitro validations. Communicated by Ramaswamy H. Sarma
Blood-based biomarkers for prediction of intracranial hemorrhage and outcome in patients with moderate or severe traumatic brain injury

BACKGROUND Early identification of traumatic intracranial hemorrhage (ICH) has implications for triage and intervention. Blood-based biomarkers were recently approved by the Food and Drug Administration (FDA) for prediction of ICH in patients with mild traumatic brain injury (TBI). We sought to determine if biomarkers measured early after injury improve prediction of mortality and clinical/radiologic outcomes compared with Glasgow Coma Scale (GCS) alone in patients with moderate or severe TBI (MS-TBI). METHODS We measured glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein-2 (MAP-2) on arrival to the emergency department (ED) in patients with blunt TBI enrolled in the placebo arm of the Prehospital TXA for TBI Trial (prehospital GCS score, 3–12; SPB, > 90). Biomarkers were modeled individually and together with prehospital predictor variables [PH] (GCS score, age, sex). Data were divided into a training data set and test data set for model derivation and evaluation. Models were evaluated for prediction of ICH, mass lesion, 48-hour and 28-day mortality, and 6-month Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). Area under the curve (AUC) was evaluated in test data for PH alone, PH + individual biomarkers, and PH + three biomarkers. RESULTS Of 243 patients with baseline samples (obtained a median of 84 minutes after injury), prehospital GCS score was 8 (interquartile range, 5–10), 55% had ICH, and 48-hour and 28-day mortality were 7% and 13%, respectively. Poor neurologic outcome at 6 months was observed in 34% based on GOS-E of 4 or less, and 24% based on DRS greater than or equal to7. Addition of each biomarker to PH improved AUC in the majority of predictive models. GFAP+PH compared with PH alone significantly improved AUC in all models (ICH, 0.82 vs. 0.64; 48-hour mortality, 0.84 vs. 0.71; 28-day mortality, 0.84 vs. 0.66; GOS-E, 0.78 vs. 0.69; DRS, 0.84 vs. 0.81, all p < 0.001). CONCLUSION Circulating blood-based biomarkers may improve prediction of neurological outcomes and mortality in patients with MS-TBI over prehospital characteristics alone. Glial fibrillary acidic protein appears to be the most promising. Future evaluation in the prehospital setting is warranted. LEVEL OF EVIDENCE Prospective, Prognostic and Epidemiological, level II.
Elevation of the Blood Glucose Level is Involved in an Increase in Expression of Sweet Taste Receptors in Taste Buds of Rat Circumvallate Papillae

The gustation system for sweeteners is well-known to be regulated by nutritional and metabolic conditions, but there is no or little information on the underlying mechanism. Here, we examined whether elevation of the blood glucose level was involved in alteration of the expression of sweet taste receptors in circumvallate papillae (CP) and sweet taste sensitivity in male Sprague-Dawley rats. Rats under 4 h-fed conditions following 18 h-fasting exhibited elevated blood glucose levels and decreased pancreatic T1R3 expression, compared to rats after 18 h-fasting treatment, and they exhibited increased protein expression of sweet taste receptors T1R2 and T1R3 in CP. Under streptozotocin (STZ)-induced diabetes mellites (DM) conditions, the protein expression levels of T1R2 and T1R3 in CP were higher than those under control conditions, and these DM rats exhibited increased lick ratios in a low sucrose concentration range in a brief access test with a mixture of sucrose and quinine hydrochloride (QHCl). These findings indicate that the elevation of blood glucose level is a regulator for an increase in sweet taste receptor protein expression in rat CP, and such alteration in STZ-induced DM rats is involved in enhancement of their sweet taste sensitivity.
Fluorescent multiplex cell rolling assay: simultaneous capturing up to seven samples in real-time using spectral confocal microscopy.

The parallel plate flow chamber assay is widely utilized to study physiological cell-cell adhesive interactions under dynamic flow that mimics the blood stream. In this technique, the cells are perfused under defined shear stresses over a monolayer of endothelial cells (expressing homing molecules eg. selectins) or a surface (expressing recombinant homing molecules). However, with the need to study multiple samples and multiple parameters per sample, using a traditional bright-field microscope-based-flow-assay allows only one sample at a time to be analyzed resulting in: high inter-experiment variability, the need for normalization, waste of materials and significant consumption of time. We developed a multiplexing approach using a three-color fluorescence staining method, which allowed for up to seven different combination signatures to be run at one time. Using this Fluorescent Multiplex Cell Rolling-(FMCR) assay each s¬¬ample is labeled with a different signature of emission wavelengths and mixed with other samples just minutes before the flow run. Subsequently, real-time images are acquired in a single ¬pass using a line-scanning spectral confocal microscope. To illustrate the glycan-dependent binding of E-selectin, a central molecule in cell migration, to its glycosylated ligands expressed on myeloid-leukemic cells in flow, the FMCR assay was used to analyze E-selectin-Ligand interactions following the addition (fucosyltransferase-treatment) or removal (deglycosylation) of key glycans on the flowing cells. The FMCR assay allowed us to analyze the cell-adhesion events from these different treatment conditions simultaneously in a competitive manner and to calculate differences in rolling frequency, velocity and tethering capability of cells under study.