julilili42/papers huggingface dataset:
Abstract 112: Brain Selective Hypothermia With Intra-arterial Cold Infusions Plus Early Normobaric Hyperoxygenation for Neuroprotection in Experimental Acute Ischemic Stroke
2019-01-30

Introduction: Characterized by strong and brain-selective cooling performance paired with only minor (systemic) adverse effects, intra-arterial cold infusions (IACI) into brain-supplying arteries have been reported as neuroprotective in experimental acute ischemic stroke (AIS). Combining normobaric hyperoxygenation (NBHO) with IACI might potentiate neuroprotection by increasing oxygen supply and, at the same time, reducing metabolism during ischemia and mitigating oxidative stress during reperfusion. Methods: To investigate potentially synergistic effects, we tested NBHO+IACI vs. NBHO vs. IACI vs. controls in a transient (60 minutes) filament middle cerebral artery occlusion (MCAO) rat model (n = 16 per group). NBHO (100 % oxygen) was initiated 10 minutes after MCAO, continuous IACI (0 °C, 12 mL) into the internal carotid artery were started two minutes prior to reperfusion, both treatments were stopped (simultaneously) after 65 and 15 minutes. Infarct and edema growth were estimated by MRI incl. perfusion, diffusion and T2 during ischemia, at 24 hours and two weeks. Neurological tests were performed for functional outcome. NeuN, IB4 and GFAP staining was used to illustrate selective neuron loss (SNL), microglia activation and gliosis at two weeks. Effect of arterial on penumbral oxygenation was evaluated with pre/post-treatment blood gas analyses and MBA1 staining at 24 hours. Results: In accordance with previous studies, NBHO reduced infarct growth (primary endpoint; T2 infarct at two weeks minus perfusion ischemic core during MCAO) by 50 % vs. controls. Cerebral edema, penumbral oxygenation and functional outcome as well as SNL, microglia activation and gliosis were also improved or reduced. In contrast, IACI were not beneficial and no synergistic neuroprotection was found for NBHO+IACI. Conclusions: Our findings confirm strong NBHO-mediated neuroprotection in AIS, while IACI were not neuroprotective. Longer duration of brain-selective hypothermia might be the key, but IACI volume is the limiting factor. MRI, functional and histological results will be discussed in the context of current literature.
Abstract TMP15: Thrombolysis in Stroke With Unknown Onset Based on Non-contrast Ct (TRUST CT). An International, Multicenter, Registry-based Study
2019-01-30

Background: Thrombolysis in wake-up stroke (WUS) or stroke with unknown onset (SUO) has been recently proven to be safe and effective using magnetic resonance imaging (MRI). However, in most of the thrombolyzing hospitals worldwide MR imaging is not available. We hypothesize that pragmatic non-contrast CT (NCCT)-based WUS/SUO thrombolysis may be feasible and safe. Methods: TRUST-CT is an international multicenter registry-based study. WUS/SUO patients undergoing NCCT-based thrombolysis with NIHSS ≥ 4 and initial ASPECTS ≥ 7 are included and compared to propensity score matched non-thrombolyzed WUS/SUO controls. Primary endpoint is symptomatic intracranial hemorrhage (ICH); secondary endpoints include 24-hour NIHSS change of ≥ 4 and modified Rankin Score (mRS) at 90 days. Results: Until now 100 patients with NCCT-based WUS/SUO thrombolysis were included. As compared to 100 controls, the median admission NIHSS was 9 and 8, respectively; the median ASPECTS was 10 in both groups. 3 (3 %) patients and 0 controls suffered symptomatic ICH. A decrease of ≥ 4 NIHSS points was observed in 48 % of the thrombolyzed patients as compared to 25% in the control group (p = 0.001); 33% and 28% achieved mRS 0 to 1 at 90 days, respectively (p = 0.4). Conclusions: NCCT-based thrombolysis in WUS/SUO seems feasible, safe and eventually effective. Updated results will be presented and discussed in the context of current evidence.
Abstract WMP83: cGMP-Dependent Protein Kinase I in Smooth Muscle Cells Protects Against Stroke in Female Mice
2019-01-30

Introduction: The role of cGMP-dependent protein kinase I (cGKI) in regulating vascular smooth muscle cells (SMC) during stroke has not been completely clarified. We showed that SMC cGKI has protective effect against stroke in male mice. To elucidate whether cGKI in SMC renders its protective effect on stroke outcome by sex-dependent mechanism, we conducted study on female mice. Animals: We used a novel tamoxifen-inducible SMC-specific gene knockout mice, that expresses CreER T2 recombinase under the control of smooth muscle alpha-actin promoter. SMA-CreER T2 _cGKIfloxflox adult 12-14 weeks-old female mice after tamoxifen (TAM) administration (100 μl TAM solution (1 mg/ml) i.p. per day for 5 consecutive days at the age 5-6 weeks) were used as experimental animals (cGKI SMKO mice). Control animals consisted of three types of female mice: (1) C57BL/6 (WT) mice without TAM treatment; (2) SMA-CreER T2 _cGKIfloxflox mice without TAM treatment (cGKI control); (3) cGKIfloxflox mice (without SMA-CreER T2 transgene) treated with TAM (cGKI control TAM). Methods: Mice (n=12/group) were anesthetized (1.5% of isoflurane in 30% of O 2 and 70% of N 2 O), body temperature was maintained (36.5-37.0 0 C) during 30-min filament-mediated middle cerebral artery occlusion (MCAO) and 30 min of reperfusion. Cerebral laser-Doppler flowmetry was utilized during the surgery to evaluate the regional cerebral blood flow (CBF). Results: The cGKI SMKO mice revealed greater cerebral infarct volume (93±12 mm 3 , Mean±SD) than WT (64±14), cGKI control (62±14), and cGKI control TAM (68±10) mice (TTC staining, indirect calculation, p&lt;0.001, one-way analysis of variance with Bonferroni correction). Neurological deficit by 4-point scale was worse in the cGKI SMKO mice (2.3 points) as compared with WT (1.5), cGKI control (1.2), and cGKI control TAM (1.3) mice (p&lt;0.05). The CBF during reperfusion was less in cGKI SMKO mice (44±19%) than in control groups (70±16 in WT; 81±33 in cGKI control; 70±19 in cGKI control TAM (15-th minute of reperfusion), p&lt; 0.05). In conclusion, cGKI in SMC protects against stroke injury in female mice in a similar way that we previously detected in male mice. These results suggest that cGKI in SMC should be targeted in studies designed to protect brain tissue against stroke.
Coloured Compounds
2019-01-30

This chapter presents presents a brilliant approach for modern isolation and structure elucidation of coloured compounds. It includes background, in-depth information about isolation processes and structural characterization as well as a Q&A section. Thymoquinone is derived from the oil of the seeds of black caraway. In the Orient the seeds of the black caraway are traditionally used as a spice, typically like sesame on pitta bread, but also as a medicine. Naturopathy has many applications for black caraway, such as cures for allergies, psoriasis, asthma and ailments connected with pregnancy. In the plant thymoquinone can be regarded to be an oxidation product of thymol. Thymol, named after thyme, has a bactericide and fungicide effect. Thymoquinone is first obtained as a component of an essential oil obtained by the steam distillation of black seed oil, then extracted from the distillate and enriched twice by column chromatography.
Carbohydrates and Glycosides
2019-01-30

This chapter presents a brilliant approach for modern isolation and structure elucidation of carbohydrates and glycosides. It includes background, in-depth information about isolation processes and structural characterization as well as a Q&A section. Raffinose is derived from the seeds of blue lupins. The properties of lupins as a soil conditioner were known to antiquity. Raffinose is a combination of three of the four most important hexoses that occur naturally, namely D-glucose, D-fructose and D-galactose. The scheme of the raffinose family of oligosaccharides raffinose, stachyose, verbascose, ajugose and higher homologues show, that with sucrose we are dealing with an increasing degree of galactosylation. Lupin flour, lupin protein concentrate, lupin bran or lupin fibre concentrate are available for the production of gluten-free bakery products and meals for the dietary treatment of patients with coeliac disease.
Aromatic Compounds
2019-01-30

This chapter presents a brilliant approach for modern isolation and structure elucidation of aromatic compounds. It includes background, in-depth information about isolation processes and structural characterization as well as a Q&A section. Sinensetin is derived from cold-pressed orange oil. Juice is the main product. Apart from this cold-pressed orange oil, a very complex dark yellow oil with an intensive aroma, can be obtained from the peel. Such a Florida orange oil contains the hydrophobic components of the peel. It served us as a source of sinensetin. On pressing orange peel all the non-polar or medium polar compounds of low molecular weight that it contains, to which sinensetin and other flavonoids belong, dissolve in limonene. Sinensetin is the only compound with an intense blue fluorescence. The band of sinensetin is scraped off with a micro-spatula and the sinensetin extracted from the stationary phase with the eluent.
Appendix
2019-01-30

4) IR spectra were recorded on a Thermo-Nicolet Avatar 360 FT-IR instrument either in KBr or as a film.Typically, the data were base line corrected.The data were obtained as WMF files and converted into emf files.(5) All NMR spectra were recorded at room temperature on Bruker DRX-400, DRX-600 or Avance-700 instruments using either inverse probe heads or in the case of the 700 MHz instrument, a cryo probe head.The experimental and the processing conditions were very similar to the experiments 1.1 -1.6 of ref. [2].The data were extracted as png files from the Bruker Topspin plot program.(6) The mass spectra were recorded in low and high resolution mode mainly on a Finnigan MAT 8230 or on a VG ZAB HSQ of VG Analytics with 70 eV excitation.The data were digitally transferred to an Excel sheet, recalculated and plotted using the Excel graphics.The ESI spectra were recorded on a Bruker FT ICR APEX-II mass spectrometer.
Quantum Chemical Calculation
2019-01-30

This chapter expresses that nuclear magnetic resonance (NMR) spectroscopy is the most important experimental technique that is used to identify natural products. Contemporary experimental NMR-spectroscopic techniques facilitate the decisive assignment of NMR spectra of small and medium sized molecules on a routine basis. Software for the empirical prediction of NMR chemical shifts is available in several programs for chemical structure drawing such as ChemBioDraw, MestReNova and some Linux software for structure drawing and is also web-based. Contrary to the purely empirical methods that predict NMR spectra, quantum chemical calculations connect the NMR parameters directly with the electronic molecular structure. The calculation of the chemical shift requires a calculation of the isotropic nuclear shielding tensor. The quantum chemical model that is the methods and basis sets used for the NMR calculation, influences the calculated values of the magnetic shielding.
Inflammatory mechanisms in neurodegeneration
2019-01-31

Abstract This review discusses the profound connection between microglia, neuroinflammation, and Alzheimer's disease ( AD ). Theories have been postulated, tested, and modified over several decades. The findings have further bolstered the belief that microglia‐mediated inflammation is both a product and contributor to AD pathology and progression. Distinct microglia phenotypes and their function, microglial recognition and response to protein aggregates in AD , and the overall role of microglia in AD are areas that have received considerable research attention and yielded significant results. The following article provides a historical perspective of microglia, a detailed discussion of multiple microglia phenotypes including dark microglia, and a review of a number of areas where microglia intersect with AD and other pathological neurological processes. The overall breadth of important discoveries achieved in these areas significantly strengthens the hypothesis that neuroinflammation plays a key role in AD . Future determination of the exact mechanisms by which microglia respond to, and attempt to mitigate, protein aggregation in AD may lead to new therapeutic strategies. image
Role of Palmitoylation of Postsynaptic Proteins in Promoting Synaptic Plasticity
2019-01-31

Many postsynaptic proteins undergo palmitoylation, the reversible attachment of the fatty acid palmitate to cysteine residues, which influences trafficking, localization, and protein interaction dynamics. Both palmitoylation by palmitoyl acyl transferases (PAT) and depalmitoylation by palmitoyl-protein thioesterases (PPT) is regulated in an activity-dependent, localized fashion. Recently, palmitoylation has received attention for its pivotal contribution to various forms of synaptic plasticity, the dynamic modulation of synaptic strength in response to neuronal activity. For instance, palmitoylation and depalmitoylation of the central postsynaptic scaffold protein postsynaptic density-95 (PSD-95) is important for synaptic plasticity. Here, we provide a comprehensive review of studies linking palmitoylation of postsynaptic proteins to synaptic plasticity.
A New Panel-Based Next-Generation Sequencing Method for ADME Genes Reveals Novel Associations of Common and Rare Variants With Expression in a Human Liver Cohort
2019-01-31

We developed a panel-based NGS pipeline for comprehensive analysis of 340 genes involved in absorption, distribution, metabolism and excretion (ADME) of drugs, other xenobiotics, and endogenous substances. The 340 genes comprised phase I and II enzymes, drug transporters and regulator/modifier genes within their entire coding regions, adjacent intron regions and 5' and 3'UTR regions, resulting in a total panel size of 1,382 kbp. We applied the ADME NGS panel to sequence genomic DNA from 150 Caucasian liver donors with available comprehensive gene expression data. This revealed an average read-depth of 343 (range 27-811), while 99% of the 340 genes were covered on average at least 100-fold. Direct comparison of variant annotation with 363 available genotypes determined independently by other methods revealed an overall accuracy of >99%. Of 15,727 SNV and small INDEL variants, 12,022 had a minor allele frequency (MAF) below 2%, including 8,937 singletons. In total we found 7,273 novel variants. Functional predictions were computed for coding variants (<i>n</i> = 4,017) by three algorithms (Polyphen 2, Provean, and SIFT), resulting in 1,466 variants (36.5%) concordantly predicted to be damaging, while 1,019 variants (25.4%) were predicted to be tolerable. In agreement with other studies we found that less common variants were enriched for deleterious variants. <i>Cis</i>-eQTL analysis of variants with (MAF ≥ 2%) revealed significant associations for 90 variants in 31 genes after Bonferroni correction, most of which were located in non-coding regions. For less common variants (MAF < 2%), we applied the SKAT-O test and identified significant associations to gene expression for <i>ADH1C</i> and <i>GSTO1</i>. Moreover, our data allow comparison of functional predictions with additional phenotypic data to prioritize variants for further analysis.
Math Anxiety in Combination With Low Visuospatial Memory Impairs Math Learning in Children
2019-01-31

Math anxiety impairs academic achievements in mathematics. According to the processing efficiency theory (PET), the adverse effect is the result of reduced processing capacity in working memory (WM). However, this relationship has been examined mostly with correlational designs. Therefore, using an intervention paradigm, we examined the effects of math anxiety on math learning. Twenty-five 5th graders underwent seven training sessions of multiplication over the course of 2 weeks. Children were faster and made fewer errors in solving trained problems than untrained problems after learning. By testing the relationship between math anxiety, WM, and math learning, we found that if children have little or no math anxiety, enough WM resources are left for math learning, so learning is not impeded. If they have high math anxiety and high visuospatial WM, some WM resources are needed to deal with math anxiety but learning is still supported. However, if they have high math anxiety and low visuospatial WM capacity, math learning is significantly impaired. These children have less capacity to learn new math content as cognitive resources are diverted to deal with their math anxiety. We conclude that math anxiety not only hinders children's performance in the present but potentially has long-lasting consequences, because it impairs not only math performance but also math learning. This intervention study partially supports the PET because only the combination of high math anxiety and low WM capacity seems critical for hindering math learning. Moreover, an adverse effect of math anxiety was observed on performance effectiveness (response accuracy) but not processing efficiency (response time).
Enamel Microabrasion and Dental Bleaching on Teeth Presenting Severe-pitted Enamel Fluorosis: A Case Report
2019-01-31

SUMMARY The present clinical case report describes the clinical steps of enamel microabrasion associated with dental bleaching to restore severely-pitted fluorosed teeth. The process of removing the fluorotic superficial stains started by using macroabrasion with a water-cooled fine tapered 3195 FF diamond bur. Rubber dam isolation of the operative field was used to remove the remaining enamel stains and superficial irregularities with the Opalustre microabrasive compound (6.6% hydrochloric acid associated with silicon carbide particles) followed by polishing using fluoridated paste and subsequent 2% neutral fluoride gel topical application. After one month, dental bleaching was performed using 10% carbamide peroxide in custom-formed acetate trays for two hours/day for 42 days. The association of enamel microabrasion with dental bleaching was effective for reestablishing the dental esthetics of a patient with severe dental fluorosis.
SGK1-dependent stimulation of vascular smooth muscle cell osteo-/chondrogenic transdifferentiation by interleukin-18
2019-01-31

The serum- and glucocorticoid-inducible kinase 1 (SGK1) is a key regulator of osteo-/chondrogenic transdifferentiation and subsequent calcification of vascular smooth muscle cells (VSMCs). The phenotypical transdifferentiation of VSMCs is associated with increased interleukin-18 (IL-18) levels and generalized inflammation. Therefore, the present study investigated the possible involvement of SGK1 in IL-18-induced vascular calcification. Experiments were performed in primary human aortic smooth muscle cells (HAoSMCs) treated with recombinant human IL-18 protein in control or high phosphate conditions and following SGK1 knockdown by siRNA or pharmacological inhibition of SGK1, PI3K, and PDK1. As a result, IL-18 treatment increased SGK1 mRNA and protein expression in HAoSMCs. IL-18 upregulated SGK1 mRNA expression in a dose-dependent manner. This effect was paralleled by upregulation of the mRNA expression of MSX2 and CBFA1, osteogenic transcription factors, and of tissue-nonspecific alkaline phosphatase (ALPL), an osteogenic enzyme, as markers of increased osteo-/chondrogenic transdifferentiation. Phosphate treatment increased SGK1 and osteogenic markers mRNA expression as well as ALPL activity and induced calcification of HAoSMCs, all effects significantly augmented by additional treatment with IL-18. Conversely, silencing of SGK1 or cotreatment with the SGK1 inhibitor EMD638683 blunted the effects of IL-18 on osteo-/chondrogenic transdifferentiation and calcification of HAoSMCs. The procalcific effects of IL-18 were similarly suppressed in the presence of PI3K or PDK1 inhibitors. In conclusion, SGK1 expression is upregulated by IL-18 in VSMCs and SGK1 participates in the intracellular signaling of IL-18-induced osteo-/chondrogenic transdifferentiation of VSMCs. Thus, SGK1 may serve as therapeutic target to limit the progression of medial vascular calcification during vascular inflammation.
Evaluation of direct costs associated with alveolar and cystic echinococcosis in Austria
2019-01-31

This study provides detailed information on direct healthcare-related costs associated with CE and AE in Austria, which may reflect trends for other high-income countries. Surgery and albendazole therapy, due to surprisingly high drug prices, were identified as important cost-drivers. These data will be important for cost-effectiveness analyses of possible prevention programs.
Phase-Separation Kinetics in Protein–Salt Mixtures with Compositionally Tuned Interactions
2019-01-31

Liquid-liquid phase separation (LLPS) in protein systems is relevant for many phenomena, from protein condensation diseases to subcellular organization to possible pathways toward protein crystallization. Understanding and controlling LLPS in proteins is therefore highly relevant for various areas of (biological) soft matter research. Solutions of the protein bovine serum albumin (BSA) have been shown to have a lower critical solution temperature-LLPS (LCST-LLPS) induceable by multivalent salts. Importantly, the nature of the multivalent cation used influences the LCST-LLPS in such systems. Here, we present a systematic ultrasmall-angle X-ray scattering investigation of the kinetics of LCST-LLPS of BSA in the presence of different mixtures of HoCl<sub>3</sub> and LaCl<sub>3</sub>, resulting in different effective interprotein attraction strengths. We monitor the characteristic length scales ξ( t, T<sub>fin</sub>) after inducing LLPS by subjecting the respective systems to temperature jumps in their liquid-liquid coexistence regions. With increasing interprotein attraction and increasing T<sub>fin</sub>, we observe an increasing deviation from the growth law of ξ ∼ t<sup>1/3</sup> and an increased trend toward arrest. We thus establish a multidimensional method to tune phase transitions in our systems. Our findings help shed light on general questions regarding LLPS and the tunability of its kinetics in both proteins and colloidal systems.