bluuebunny/crossref_metadata_2025 huggingface dataset:
Focal adhesion kinase confers pro‐migratory and antiapoptotic properties and is a potential therapeutic target in Ewing sarcoma
Authors: Steinestel Konrad , Trautmann Marcel , Jansen Esther‐Pia , Dirksen Uta , Rehkämper Jan , Mikesch Jan‐Henrik , Gerke Julia S. , Orth Martin F. , Sannino Giuseppina , Arteaga Maria‐Francisca , Rossig Claudia , Wardelmann Eva , Grünewald Thomas G. P. , Hartmann Wolfgang
Published: December 2019

Oncogenesis of Ewing sarcoma (EwS), the second most common malignant bone tumor of childhood and adolescence, is dependent on the expression of chimeric EWSR1‐ETS fusion oncogenes, most often EWSR1‐FLI1 (E/F). E/F expression leads to dysregulation of focal adhesions (FAs) enhancing the migratory capacity of EwS cells. Here, we show that, in EwS cell lines and tissue samples, focal adhesion kinase (FAK) is expressed and phosphorylated at Y397 in an E/F‐dependent way involving Ezrin. Employing different EwS cell lines as in vitro models, we found that key malignant properties of E/F are mediated via substrate‐independent autophosphorylation of FAK on Y397. This phosphorylation results in enhanced FA formation, Rho‐dependent cell migration, and impaired caspase‐3‐mediated apoptosis in vitro. Conversely, treatment with the FAK inhibitor 15 (1,2,4,5‐benzenetetraamine tetrahydrochloride (Y15) enhanced caspase‐mediated apoptosis and EwS cell migration, independent from the respective EWSR1‐ETS fusion type, mimicking an anoikis‐like phenotype and paralleling the effects of FAK siRNA knockdown. Our findings were confirmed in vivo using an avian chorioallantoic membrane model and provide a first rationale for the therapeutic use of FAK inhibitors to impair metastatic dissemination of EwS.
Well‐defined N‐heterocyclic carbene/ruthenium complexes for the alcohol amidation with amines: The dual role of cesium carbonate and improved activities applying an added ligand
Authors: Wang Wan‐Qiang , Yuan Ye , Miao Yang , Yu Bao‐Yi , Wang Hua‐Jing , Wang Zhi‐Qin , Sang Wei , Chen Cheng , Verpoort Francis
Published: December 2019

Dehydrogenative amide bond formation from alcohols and amines has been regarded as an atom‐economic and sustainable process. Among various catalytic systems, N‐heterocyclic carbene (NHC)‐based Ru catalytic systems have attracted growing interest due to the outstanding properties of NHCs as ligands. Herein, an NHC/Ru complex (1) was prepared and its structure was further confirmed with X‐ray crystallography. In the presence of Cs2CO3, two NHC/Ru‐based catalytic systems were disclosed to be active for this amide synthesis. System A, which did not contain any added ligand, required a catalyst loading of 1.00 mol%. Interestingly, improved catalytic performance was realized by the addition of an NHC precursor (L). Optimization of the amounts of L and other conditions gave rise to system B, a much more potent system with the Ru loading as low as 0.25 mol%. Moreover, an NHC‐Ru‐carbonate complex 6 was identified from the refluxing toluene of 1 and Cs2CO3, and further investigations revealed that 6 was an important intermediate for this catalytic reaction. Based on the above results, we claimed that the role of Cs2CO3 was to facilitate the formation of key intermediate 6. On the other hand, it provided the optimized basicity for the selective amide formation.
Mechanism and influence factors of 2,4‐D dechlorination by sodium citrate‐activated bimetallic palladium‐zero valent iron nanoparticles
Authors: Zhou Hongyi , Zhao Yongkang , Xiang Junchao , Huang Ning , Baig Shams Ali , Zeng Sisi
Published: December 2019

Nanoscale zero‐valent iron (nZVI) has high removal efficiency and strong reductive ability to organic contaminants, but this reactivity soon ceases and is attributed to rapid passivation of the nZVI surface due to the formation of iron oxides. In the present study, bimetallic palladium‐zero valent iron nanoparticles were activated with sodium citrate (SC‐nPd/Fe) to enhance 2,4‐D dechlorination from aqueous solutions. FTIR and XRD analyses showed that there was no passivation layer on the surface of nZVI after the addition of SC, and XPS analysis confirmed the nZVI after the reaction still maintained high reactivity and surface Pd ratio. The existence of SC facilitated the transfer of electrons from Fe0 to contaminants, thus accelerating the reductive dechlorination of 2,4‐D. The dechlorination efficiency of 2,4‐D on nPd/Fe was only 56.4% in 210 min, while complete dechlorination could be achieved on SC‐nPd/Fe under the same conditions, and simultaneously 97.1% of phenoxyacetic acid (PA) was generated. Moreover, the effect of reaction conditions on the dechlorination such as Pd ratio, SC dosage, initial pH and temperature was also investigated, and it was well described by pseudo‐first‐order kinetic model. In particular, The chelating abilities of SC is similar to EDTA, but it is an environmentally‐friendly chelating agent. Findings from the present study suggested that the SC could be a promising substitute for application in the remediation of 2,4‐D contained water.
Fourteen polymorphic microsatellite markers for the widespread Labrador tea (Rhododendron groenlandicum)
Authors: Sheik Matthew L. , LaBounty Kitty L. , Mitchell Erika , Gillespie Emily L.
Published: December 2019

Premise

Microsatellite markers were developed for Labrador tea (Rhododendron groenlandicum, Ericaceae) to facilitate downstream genetic investigation of this species and the extremely closely related, circumboreal Rhododendron subsect. Ledum.

Methods and Results

Forty‐eight primer pairs were designed using Illumina data and screened for excellent amplification. Sixteen successful pairs were developed as microsatellite markers using fluorescently labeled amplification to generate chromatogram data. These data were evaluated for intrapopulation and interpopulation variability in three populations from Alaska and Maine, USA, and the Northwest Territories, Canada. Fourteen polymorphic markers genotyped reliably, each with one to eight alleles. Cluster analysis indicates that across the range, populations can be easily discriminated. Cross‐amplification in other Rhododendron subsect. Ledum species shows broad application of the developed markers within this small, well‐supported clade.

Conclusions

These microsatellite markers exhibit significant variability and will be useful in population genetics within R. groenlandicum and for investigation of species boundaries across Rhododendron subsect. Ledum.
Microsatellite markers for the endangered Puya raimondii in Peru
Authors: Tumi Liscely , Zhang Yu‐Qu , Wang Zheng‐Feng , Suni Mery L. , Burgess Kevin S. , Ge Xue-jun
Published: December 2019

Premise

Microsatellite primers were developed for Puya raimondii (Bromeliaceae), an endangered species distributed in the Andean Mountains of Bolivia and Peru.

Methods and Results

Genome skimming of P. raimondii, P. macrura, and P. hutchisonii resulted in the selection of 46 pairs of cross‐species microsatellite markers. Of these, 12 microsatellite primer pairs produced clear and polymorphic bands in P. raimondii. These primer sets were then used for the detection of potential polymorphisms in 84 P. raimondii individuals collected from four populations in Peru. The number of alleles per locus ranged from one to six, and the observed and expected levels of heterozygosity ranged from 0.000 to 0.8929 and from 0.000 to 0.7662, respectively.

Conclusions

The microsatellite markers developed in this study will be useful for future population genetic analyses and breeding system studies in P. raimondii.
Glucose–methanol‐based fed‐batch fermentation for the production of recombinant human interferon gamma (rhIFN‐γ) and evaluation of its antitumor potential
Authors: Prabhu Ashish A , Kumar Jadi Praveen , Mandal Biman B. , Veeranki Venkata Dasu
Published: December 2019

Squamous cell carcinoma (SCC) is nonmelanoma skin cancer, which is very common in patients having T‐cell immunosuppressant drugs. Anticancerous agents such as cytokines showed effective response on SCC. Human interferon‐gamma (hIFN‐γ), a type II cytokines, are having potent antiproliferative and immunomodulatory effects. In the current study, the fed‐batch cultivation of recombinantPichia pastoriswas carried out, and its effect on cell biomass production, recombinant human interferon‐gamma (rhIFN‐γ) production, and the overflow metabolites was estimated.P. pastorisGS115 strain coexpressed with 6‐phosphogluconolactonase (SOL3) and ribulose‐phosphate 3‐epimerase (RPE1) gene (GS115/rhIFN‐γ/SR) resulted in 60 mg L−1of rhIFN‐γ production, which was twofold higher as compared with the production from GS115/rhIFN‐γ strain. The antiproliferative potential of rhIFN‐γ was examined on the human squamous carcinoma (A431) cell lines. Cells treated with 80 ng mL−1of rhIFN‐γ exhibited 50% growth inhibition by enhancing the production of intracellular reactive oxygen species levels and disrupting membrane integrity. Our findings highlight a state of art process development strategy for the high‐level production of rhIFN‐γ and its potential application as a therapeutic drug in SCC therapy.
Helpfulness and economic impact of multidimensional rating systems: Perspective of functional and hedonic characteristics
Authors: Kong Demei , Yang Jun , Duan Hongchen , Yang Siyue
Published: December 2019

Nowadays, the multidimensional rating systems are increasingly popular in practice to help consumers evaluate multiattribute products or services. This study aims to examine the helpfulness and economic impact of multidimensional rating systems and the moderating effect of product type (ordinary, premium) from the perspective of product line. To identify the different effects of different product characteristics on consumers' behavior, multidimensional ratings and textual reviews are classified into two different sets according to the product attributes (functional, hedonic). Besides, the effects of review valence are considered simultaneously. Econometric analysis and text mining are conducted on the real data from autohome.com, a leading Chinese automobile rating platform. Results show that (a) in terms of perceived helpfulness, reviews with positive functional ratings or with negative hedonic ratings are perceived more helpful for ordinary product, whereas reviews with positive hedonic ratings are perceived more helpful for premium product. (b) Regarding product sales, the impacts of functional and hedonic ratings on product sales are inverted U‐shape. Furthermore, for ordinary product, variance of functional ratings has a negative effect on product sales, whereas hedonic ratings variance has an opposite impact. Surprisingly, ordinary product consumers tend to pay more attention to the negative hedonic reviews, whereas premium product consumers concentrate more on the negative functional reviews. In summary, various influences of multidimensional reviews and ratings across product type on review helpfulness and product sales are deeply explored in this study, suggesting that firms' online marketing strategies should be contingent on product type and characteristics.
Fractionation and characterization of antioxidant peptides from rice bran protein hydrolysates stimulated by in vitro gastrointestinal digestion
Authors: Phongthai Suphat , Rawdkuen Saroat
Published: December 2019

Background and objective

Rice bran protein concentrate was prepared and hydrolyzed by using pepsin–pancreatin. The obtained result was further filtered through 5‐kDa membranes. A permeate was collected and sequentially fractionated by different chromatographic techniques. The peptide fractions were determined for the antioxidant activities.

Findings

Three peptide fractions were derived after separating the crude protein hydrolysates by anion‐exchange chromatography. Due to its highest ABTS radical scavenging and metal chelating activities (p < .05), fraction F2‐A was pooled and separated further by size‐exclusion chromatography (SEC). Among the SEC fractions, F1‐S showed strongest antioxidant activities; thus, it was collected for reverse‐phase HPLC purification. Subsequently, the peptide fractions were successfully separated and F4‐H had the greatest ABTS‐scavenging activities (214.61 µmol Trolox/g sample, respectively). In addition, it displayed the strongest ability to reduce ferric to ferrous ions (104.80 µmol FeSO4/g sample) (p < .05), while F1‐H showed the highest ability to chelate metal ions (266.40 µmol EDTA/g sample) (p < .05).

Conclusion

These results demonstrate that hydrophobic amino acids play a major role in scavenging free radicals, whereas polar amino acids are responsible for reducing and chelating metal ions.

Significance and novelty

Rice bran protein composes of high ratio of hydrophobic amino acid. It is a suitable source of antioxidant peptides that might be produced during gastrointestinal digestion. Separation and purification using chromatographic techniques showed promising results for selectively fractionate antioxidant peptides with specific activity.
Profilin as a dual regulator of actin and microtubule dynamics
Authors: Pinto‐Costa Rita , Sousa Mónica M.
Published: December 2019

Although originally identified as G‐actin sequestering proteins, profilins are emerging as critical regulators of actin dynamics, capable of interacting with multiple acting binding proteins, and being able to link membrane lipids to cytoskeleton components. Recently, in addition to its actin, poly‐proline, and phosphatidylinositol binding domains, profilin has been shown to contain residues specialized in microtubule binding. Here we will discuss in a critical perspective the emerging body of data supporting that profilins are central mediators of actin microfilament and microtubule interaction. We will also address the unanswered questions in the field, including the nature of the interaction of profilin with microtubules, and its effect on microtubule dynamics. These recent discoveries deepen our understanding on how different cytoskeleton components are integrated within cells.
Inner retinal preservation in the photoinducible I307N rhodopsin mutant mouse, a model of autosomal dominant retinitis pigmentosa
Authors: Stefanov Antonia , Novelli Elena , Strettoi Enrica
Published: December 2019

Rod‐cone degenerations, for example, retinitis pigmentosa are leading causes of blindness worldwide. Despite slow disease progression in humans, vision loss is inevitable; therefore, development of vision restoration strategies is crucial. Among others, promising approaches include optogenetics and prosthetic implants, which aim to bypass lost photoreceptors (PRs). Naturally, the efficacy of these therapeutic strategies will depend on inner retinal structural and functional preservation. The present study shows that in photoinducible I307N rhodopsin mice (Translational Vision Research Model 4 [Tvrm4]), a 12k lux light exposure eliminates PRs in the central retina in 1 week, but interneurons and their synapses are maintained for as long as 9 weeks postinduction. Despite bipolar cell dendritic retraction and moderate loss of horizontal cells, the survival rate of various cell types is very high. Significant preservation of conventional synapses and gap junctions in the inner plexiform layer is also observed. We found the number of synaptic ribbons to gradually decline and their ultrastructure to become transiently abnormal, although based on our findings intrinsic retinal architecture is maintained despite complete loss of PRs. Unlike common rodent models of PR degeneration, where the disease phenotype often interferes with retinal development, in Tvrm4 mice, the degenerative process can be induced after retinal development is complete. This time course more closely mimics the timing of disease onset in affected patients. Stability of the inner retina found in these mutants 2 months after PR degeneration suggests moderate, stereotyped remodeling in the early stages of the human disease and represents a promising finding for prompt approaches of vision restoration.
Role of High‐Throughput Electrophysiology in Drug Discovery
Authors: Liu Chang , Li Tianbo , Chen Jun
Published: December 2019

Due to their important physiological functions, ion channels are key therapeutic targets for a variety of disorders. However, electrophysiological assessment of ion channel activity is technically challenging and has been a bottleneck in the discovery of drugs that modulate channel function. To address this issue, automated patch clamp platforms have been developed with improved throughput and broader applications. An overview of the current status of high‐throughput electrophysiology and its applications in drug discovery is provided. © 2019 The Authors.
Dynamic response in the larval geoduck (Panopea generosa) proteome to elevated pCO2
Authors: Timmins‐Schiffman Emma , Guzmán José M. , Elliott Thompson Rhonda , Vadopalas Brent , Eudeline Benoit , Roberts Steven B.
Published: December 2019

Pacific geoducks (Panopea generosa) are clams found along the northeast Pacific coast where they are important components of coastal and estuarine ecosystems and a major aquaculture product. The Pacific coastline, however, is also experiencing rapidly changing ocean habitat, including significant reductions in pH. To better understand the physiological impact of ocean acidification on geoduck clams, we characterized for the first time the proteomic profile of this bivalve during larval development and compared it to that of larvae exposed to low pH conditions. Geoduck larvae were reared at pH 7.5 (ambient) or pH 7.1 in a commercial shellfish hatchery from day 6 to day 19 postfertilization and sampled at six time points for an in‐depth proteomics analysis using high‐resolution data‐dependent analysis. Larvae reared at low pH were smaller than those reared at ambient pH, especially in the prodissoconch II phase of development, and displayed a delay in their competency for settlement. Proteomic profiles revealed that metabolic, cell cycle, and protein turnover pathways differed between the two pH and suggested that differing phenotypic outcomes between pH 7.5 and 7.1 are likely due to environmental disruptions to the timing of physiological events. In summary, ocean acidification results in elevated energetic demand on geoduck larvae, resulting in delayed development and disruptions to normal molecular developmental pathways, such as carbohydrate metabolism, cell growth, and protein synthesis.
Phenotypic plasticity, but not adaptive tracking, underlies seasonal variation in post‐cold hardening freeze tolerance of Drosophila melanogaster
Authors: Stone Helen M. , Erickson Priscilla A. , Bergland Alan O.
Published: December 2019

In temperate regions, an organism's ability to rapidly adapt to seasonally varying environments is essential for its survival. In response to seasonal changes in selection pressure caused by variation in temperature, humidity, and food availability, some organisms exhibit plastic changes in phenotype. In other cases, seasonal variation in selection pressure can rapidly increase the frequency of genotypes that offer survival or reproductive advantages under the current conditions. Little is known about the relative influences of plastic and genetic changes in short‐lived organisms experiencing seasonal environmental fluctuations. Cold hardening is a seasonally relevant plastic response in which exposure to cool, but nonlethal, temperatures significantly increases the organism's ability to later survive at freezing temperatures. In the present study, we demonstrate seasonal variation in cold hardening in Drosophila melanogaster and test the extent to which plasticity and adaptive tracking underlie that seasonal variation. We measured the post‐cold hardening freeze tolerance of flies from outdoor mesocosms over the summer, fall, and winter. We bred outdoor mesocosm‐caught flies for two generations in the laboratory and matched each outdoor cohort to an indoor control cohort of similar genetic background. We cold hardened all flies under controlled laboratory conditions and then measured their post‐cold hardening freeze tolerance. Comparing indoor and field‐caught flies and their laboratory‐reared G1 and G2 progeny allowed us to determine the roles of seasonal environmental plasticity, parental effects, and genetic changes on cold hardening. We also tested the relationship between cold hardening and other factors, including age, developmental density, food substrate, presence of antimicrobials, and supplementation with live yeast. We found strong plastic responses to a variety of field‐ and laboratory‐based environmental effects, but no evidence of seasonally varying parental or genetic effects on cold hardening. We therefore conclude that seasonal variation in post‐cold hardening freeze tolerance results from environmental influences and not genetic changes.
A practical introduction to sequentially Markovian coalescent methods for estimating demographic history from genomic data
Authors: Mather Niklas , Traves Samuel M. , Ho Simon Y. W.
Published: December 2019

A common goal of population genomics and molecular ecology is to reconstruct the demographic history of a species of interest. A pair of powerful tools based on the sequentially Markovian coalescent have been developed to infer past population sizes using genome sequences. These methods are most useful when sequences are available for only a limited number of genomes and when the aim is to study ancient demographic events. The results of these analyses can be difficult to interpret accurately, because doing so requires some understanding of their theoretical basis and of their sensitivity to confounding factors. In this practical review, we explain some of the key concepts underpinning the pairwise and multiple sequentially Markovian coalescent methods (PSMC and MSMC, respectively). We relate these concepts to the use and interpretation of these methods, and we explain how the choice of different parameter values by the user can affect the accuracy and precision of the inferences. Based on our survey of 100 PSMC studies and 30 MSMC studies, we describe how the two methods are used in practice. Readers of this article will become familiar with the principles, practice, and interpretation of the sequentially Markovian coalescent for inferring demographic history.
Recognition of big data mixed Raman spectra based on deep learning with smartphone as Raman analyzer
Authors: Liang Jie , Mu Taotao
Published: December 2019

Raman spectral detection has emerged as a powerful analytical technique due to the advantages of fast acquisition, non‐invasion, and low cost. The on‐site application is highly dependent on Raman automatic analysis algorithm. However, current Raman algorithm research mainly focuses on small sample Raman spectroscopy (RS) identification with defects of low accuracy and detection rate. It is also difficult to realize rapid RS measurement under big data. In this paper, rapid recognition of mixtures in complex environments was realized by establishing a fast Raman analysis model based on deep learning through data training, self‐learning, and parameter optimization. The cloud network architecture was proposed to apply deep learning to real‐time detection using Smartphone‐based Raman devices. This research solves the technical problems about mixture recognition under big data and thus could be used as a new method for fast and field RS detection in complex environments.
Facile Synthesis of Flock‐Like V2O3/C with Improved Electrochemical Performance as an Anode Material for Li‐Ion Batteries
Authors: Meng Leichao , Guo Ruisong , Li Fuyun , Ma Yuanliang , Peng Jianhong , Li Tingting , Luo Yani , Li Youzhen , Sun Xiaohong
Published: December 2019

V2O3is considered to be a potential anode material due to its large specific capacity and rich resources. Herein, flock‐like V2O3coated with carbon is prepared through a facile and simple solvothermal method followed by annealing at a relatively low temperature. The structure of V2O3/C is composed of porous strips. Due to the unique morphology and structure, the V2O3/C anode material shows excellent electrochemical performance. It delivers a specific discharge capacity of 696 mAh g−1after 100 cycles, which is 95% of the specific discharge capacity (732 mAh g−1) after the sixth cycle. The V2O3/C anode material annealed at 360 °C (V2O3/C‐360) delivers 601 mAh g−1at a current density of 300 mA g−1after 500 cycles. It implies superior cyclic stability of V2O3/C‐360. In addition, the anode also shows excellent rate capability. Specific capacities of approximately 600, 420, and 300 mAh g−1are obtained at the current densities of 0.3, 2, and 5 A g−1, respectively. The large current contribution of the capacitive reveals favorable superior lithium storage kinetics. This anode material presents great application potential in high‐performance lithium‐ion batteries.
Enhanced connectivity for nodes to measure coverage range using anchor node–based PATH monitoring algorithm in WSN
Authors: Anshad A.S. , Radhakrishnan R.
Published: December 2019

Wireless sensor nodes are mainly deployed to focus the coverage and connectivity between the sensor nodes. Generally, nodes coverage range is fixed, sometimes which are placed in more distance cause out of coverage range from sender node to destination node. The network does not have any path analyzer node. This drawback is overcome by the proposed research work. After analyzing the number of packet drops during the transmission, the network identifies the out of coverage range among sensor node. It reduces packet delivery ratio and network connectivity ratio. Therefore, the proposed enhanced connectivity for nodes to measure coverage range (ECCR) is used to provide better coverage–based communication among sensor nodes. Affected routing path is detected initially since alert message packet is forwarded from the source node to the destination node. Anchor node–based path monitoring algorithm is constructed to monitor abnormal activities of each sensor nodes which are placed in the network environment. The abnormal activities indicate the more packet drop during communication since its coverage range goes out of limit. It increases the connectivity ratio and packet delivery ratio.
Revisiting trainee reactions: A multilevel analysis of the nomological network
Authors: Kim Sehoon , Park Soyoun , Lavelle John , Kim Minjung , Chaudhuri Sanghamitra
Published: December 2019

Surveying participants' reactions remains the most popular approach to evaluate training programs. However, it is unclear how reactions are related to training contexts and outcomes. Using a multilevel analysis, this study examined the structural relationships among individual/situational characteristics, trainee reactions, and training outcomes in mandatory safety and health training programs. We analyzed data from 545 participants of 29 face‐to‐face training classes who completed three sequential surveys. The results revealed that pre‐training motivation and the classroom setting are associated with reactions, and reactions are associated with participatory behavior, cognitive learning, and perceived transfer. Trainee reactions significantly mediated the relationships of pre‐training motivation and the classroom setting with training outcomes. The significance of this study is identifying the roles of trainee reactions in training, applying a multilevel analysis in training research.
The pre‐gestational triglycerides and high‐density lipoprotein cholesterol ratio is associated with adverse perinatal outcomes: A retrospective cohort analysis
Authors: Arbib Nissim , Pfeffer‐Gik Tamar , Sneh‐Arbib Orly , Krispin Eyal , Rosenblat Orgad , Hadar Eran
Published: December 2019

Objective

To investigate associations between pre‐gestational dyslipidemia, expressed as the ratio between triglycerides (TG) and high‐density lipoprotein cholesterol (HDL), and adverse maternal and neonatal outcomes.

Methods

A retrospective cohort analysis included women with TG and HDL measurements available up to 52 weeks before conception who delivered a singleton, non‐anomalous infant. The study population was stratified according to a TG/HDL ratio cutoff of 3. Primary maternal outcomes included gestational diabetes or hypertensive disorders of pregnancy and neonatal outcomes after delivery before 37 weeks.

Results

Among 5226 women included, 4446 (85.1%) had TG/HDL <3 and 780 (14.9%) ≥3. TG/HDL ratio ≥3 vs <3 was associated with higher rates of gestational diabetes (13.1% vs 5.2%, P<0.0001) and hypertensive disorders of pregnancy (5.3% vs 2.2%, P<0.0001). Larger babies (3229.7 ± 520.7 g vs 3181.7 ± 504.4 g, P=0.015) with higher birth weight percentile (59.0 ± 26.4 vs 55.1 ± 26.6, P<0.0001) and increased rates of large‐for‐gestational‐age (14.5% vs 10.8%, P=0.007) and macrosomia (5.6% vs 3.9%, P=0.026) were found. In multivariate analysis, TG/HDL ≥3 remained an independent risk‐factor for gestational diabetes (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.02–2.39) and pre‐eclampsia (aOR 3.02, 95% CI 1.82–5.01).

Conclusions

An increase in adverse pregnancy outcomes was reported, mainly gestational diabetes and pre‐eclampsia, when TG/HDL ratio up to 1 year before pregnancy was ≥3.
Establishing a reference range for thromboelastography maximum amplitude in patients administrating with antiplatelet drugs
Authors: Shen Wei , Zhou Jing‐Yi , Gu Yi , Shen Wen‐Yan , Li Min
Published: December 2019

Objective

We aimed to establish the reference range of thromboelastograph (TEG) maximum amplitude (MA) in patients taking antiplatelet drugs.

Methods

Between August 2015 and July 2018, a total of 4614 patients administrating with antiplatelet drugs (clopidogrel and aspirin) were retrospectively analyzed in this study. For MAA parameter, we used the 10th and 90th percentiles to establish a reference range. The Spearman correlation was used for the correlation analysis among the inhibition rate of adenosine diphosphate (ADP%) and MAADP, inhibition rate of arachidonic acid (AA%) and MAAA. Then, through receiver operating characteristic (ROC) curve analysis of the best cutoff point, the reference ranges of MAADP and MAAA could be deduced. Consistency evaluation was performed by statistical analysis of ADP% and MAADP, AA% and MAAA pairing for 4459 patients.

Results

The reference range of MAA was 8.1‐25.8 mm. The reference range of MAADP was 19.8‐43.2 mm, and the corresponding sensitivity of two endpoints was 0.796, 0.856 and specificity were 0.897, 0.904, respectively. The reference range of MAAA was 18.9‐37.7 mm, and the corresponding sensitivity of two endpoints was 0.819, 0.829 and specificity were 0.922, 0.896, respectively. The inconsistency rate of ADP% and MAADP, and AA% and MAAA was 20.1% (898 cases) and 16.6% (738 cases), respectively.

Conclusions

The reference range of MAADP and MAAA established by us were better in sensitivity and specificity. MAADP and MAAA were more accurate than conventional inhibition rate analysis in guidance of antiplatelet therapy, especially in patients with excessive low MA or high MAA.
A preliminary evaluation of treatment duration on the resurgence of destructive behavior
Authors: Greer Brian D. , Fisher Wayne W. , Retzlaff Billie J. , Fuhrman Ashley M.
Published: December 2019

Quantitative models of resurgence (e.g., Behavioral Momentum Theory, Resurgence as Choice) suggest that resurgence is partly a function of the duration of extinction exposure, with longer histories of extinction producing less resurgence. This prediction is supported by some laboratory research and has been partially supported by clinical translations that did not isolate the effects of extinction exposure prior to testing for resurgence. The degree to which different histories of extinction impact the likelihood of treatment relapse in therapeutic applications of differential reinforcement is of great interest to the clinical community, including insurance carriers and other financial providers. In the present study, we isolated the effects of extinction history for severe destructive behavior across 6 participants referred for treatment services and examined resurgence of destructive behavior when alternative reinforcement terminated. Our within‐subject evaluation showed no difference in the level of resurgence or persistence of destructive behavior following short and long exposures to differential reinforcement with extinction. We discuss our failure to replicate in relation to experimental‐design considerations for investigating this and other relapse phenomena in future research with clinical populations.
An efficient one‐pot synthesis of N‐(substituted phenyl)‐1,2,5‐thiadiazolidine‐2‐carboxamide 1,1‐dioxide derivatives
Authors: Hessainia Sihem , Boukhari Abbes , Cheraiet Zinelaabidine
Published: December 2019

1,2,5‐Thiadiazolidine‐1,1‐dioxide carboxamide derivatives 3a‐3n are novel heterocyclic compounds synthesized by multicomponent condensation reaction in one pot of aniline, chlorosulfonyl isocyanate, and 2‐chloroethylamine hydrochloride which is used as a useful precursor under mild conditions. This reaction is realized with high atom economy, at room temperature and in a short reaction time. Series of these desired products are obtained from good to excellent yields within 2 hours in all cases. All the synthesized compounds are characterized by 1H, 13C NMR, MS, and HMBC/HSQC spectroscopy.
Amine‐carbon disulfide promoted synthesis of novel benzo[e][1,3]thiazepin‐5(1H)‐one derivatives
Authors: Asgari Mohammad Sadegh , Bahadorikhalili Saeed , Asadi Mehdi , Rashidi Ranjbar Parviz , Larijani Bagher , Rahimi Rahmatollah , Mahdavi Mohammad
Published: December 2019

In this paper, a simple method is introduced for the synthesis of novel 4‐substituted‐3‐thioxo‐3,4‐dihydrobenzo[e][1,3]thiazepin‐5(1H)‐one derivatives. The synthesis is based on a two‐step reaction of 2‐methylbenzoic acid, an amine, and carbon disulfide. In the first step, 2‐methylbenzoic acid reacts with sulfuric acid in ethanol, followed by the reaction with N‐bromosuccinimide to produce ethyl 2‐(bromomethyl)benzoate. Amine and carbon disulfide react in a separate flask in basic medium to give carbamodithioate salt. Carbamodithioate and ethyl 2‐(bromomethyl)benzoate react together in dimethylformamide to produce the desired 4‐substituted‐3‐thioxo‐3,4‐dihydrobenzo[e][1,3]thiazepin‐5(1H)‐one derivatives. The method is simple and fast and is applicable to a wide variety of substrates and gives the desired products in high isolated yields.
Synthesis of fused hydroxy dihydropyrroles and unexpected dihydropyrazine and dihydroquinoxaline derivatives based on heterocyclic ketene aminals
Authors: Rezaei Monireh , Bayat Mohammad , Notash Behrouz
Published: December 2019

The one‐pot four‐component synthesis of highly functionalized fused hydroxyl dihydropyrroles and dihydropyrazines from readily available diamines, 1,1‐bis (methylsulfanyl)‐2‐nitroethene, phenylglyoxal monohydrates, and C‐H acids have been developed. This strategy provides an efficient, catalyst‐free approach for easy access to various new hydroxyl‐dihydropyrrole and dihydropyrazine rings in good to high yields. The products were confirmed by 1H and 13C NMR, IR, mass, and X‐ray crystal structure analyses.
Adjunctive use of enamel matrix derivatives to porcine‐derived xenograft for the treatment of one‐wall intrabony defects: Two‐year longitudinal results of a randomized controlled clinical trial
Authors: Lee Jae‐Hong , Kim Do‐Hyung , Jeong Seong‐Nyum
Published: December 2019

Background

The purpose of this study was to evaluate the potential advantages of adjunctive use of enamel matrix protein derivative (EMD) in combination with demineralized porcine bone matrix (DPBM) for the treatment of one‐wall intrabony defects in the molar regions, in comparison with the use of DPBM alone, through a randomized controlled clinical trial.

Methods

Forty‐two participants were randomly assigned to two groups: one where DPBM with the adjunctive use of EMD (test group, n = 20) was applied and the other without EMD (control group, n = 22). Changes in the clinical and radiographic parameters from baseline at 6, 12, and 24 months were measured (probing pocket depth, clinical attachment loss, defect depth, and defect width). Postoperative discomfort (severity/duration of pain and swelling) and early soft tissue wound healing (dehiscence/fenestration, persistent swelling, spontaneous bleeding, and ulceration) were also assessed.

Results

Both treatment modalities, with and without EMD, resulted in significant improvement of clinical and radiographic outcomes without any severe adverse events. However, no statistically significant differences in any of the measured parameters were found when the two groups were compared. Early wound healing outcomes and the severity of swelling did not differ between the groups, but the severity of pain (P = 0.046), duration (P = 0.033), and swelling (P = 0.022) were significantly lower in the test group.

Conclusions

DPBM has been verified for biocompatibility and can be used as a scaffold to enhance the clinical and radiographic outcomes of periodontal regeneration of one‐wall intrabony defects. In particular, the adjunctive use of EMD significantly reduced the postoperative discomfort.
The variation of the chemical composition of the main plant species in a subalpine grassland in northwestern Greece
Authors: Koutsoukis Charalampos , Roukos Christos , Demertzis Panagiotis G. , Kandrelis Sotirios , Akrida‐Demertzi Konstantoula
Published: December 2019

This study presents the results of a survey conducted in the year 2013 in a subalpine grassland located in Epirus, in northwestern Greece, and concerns the determination of the chemical composition of nine wild plants species (Alopecurus gerardii V., Stipa pennata L., Phleum alpinum L., Trifolium repens L., Lathyrus aphaca L., Lotus corniculatus L., Ranunculus repens L., Achillea millefolium L., and Geranium lucidum L.) at various stages of growth. The highest mean neutral detergent fiber content was determined in S. pennata L. samples with 546 g kg−1 dry matter (DM). The highest mean acid detergent fiber content was determined in samples of A. gerardii L. with 358 g kg−1 DM. For calcium (Ca), the highest average content was determined in the samples of L. corniculatus L. with 9.6 g kg−1 DM. For phosphorus (P), iron (Fe), and copper (Cu), the highest average contents were determined in the samples of R. repens L. with 2.8 g kg−1 DM, 60.2 mg kg−1, and 5.6 mg kg−1 DM, respectively. For magnesium (Mg), the higher average content was found in L. aphaca L. samples with 1.6 g kg−1, for potassium (K) in G. lucidum L. samples with 15.6 g kg−1, for sodium (Na) in A. millefolium L. samples with 15.3 g kg−1, and for manganese (Mn) in P. alpinum L. samples with 37.9 mg kg−1. The chemical composition of plant species meets the nutritional requirements of grazing animals in the investigated area. Among the plant species, legumes and other forbs have the highest nutritional value.
Localization of Salivary Glands for Botulinum Toxin Treatment: Ultrasound Versus Landmark Guidance
Authors: Loens Sebastian , Brüggemann Norbert , Steffen Armin , Bäumer Tobias
Published: December 2019

Background

Sialorrhea is a troublesome symptom in a variety of neurological diseases. Recently, local injection of botulinum toxin into the salivary glands was approved for treatment of sialorrhea, and injection guidance by anatomical landmarks was suggested.

Objective

To compare the accuracy of ultrasound versus previously proposed anatomical landmarks for localizing the salivary glands.

Methods

In a cross‐sectional study in 21 adults, landmark positions (LM) of the parotid gland (PG) and the submandibular gland (SG) were identified following published recommendations. The ultrasound position (US) was defined as the position representing the maximum gland thickness. The distance between positions, gland thickness, and optimal injection depth were recorded by US.

Results

Gland thickness differed significantly between LM and US positions (PG, 4 vs. 17.8 mm; P < 0.001; SG, 3.5 vs. 13.6 mm; P < 0.001). The spatial deviation between the recommended LM and identified US positions in the horizontal plane was 21 mm to the posterior direction for the PG and 19.6 mm for the SG. The deviation in vertical orientation was small for both glands; however, there was a positive correlation between the distance from the SG to the mandibular bone with age. The optimal injection depth measured by US was 11.8 mm for the PG and 13.6 mm for the SG. This showed to be positively correlated with the body mass index.

Conclusions

The position of the salivary glands differs from proposed landmarks and depends on the individual age and body weight; therefore, we recommend ultrasound guidance for injection.
Nosology and Phenomenology of Psychosis in Movement Disorders
Authors: Rossi Malco , Farcy Nicole , Starkstein Sergio E. , Merello Marcelo
Published: December 2019

Background

Psychotic symptoms, such as delusions and hallucinations, are part of the clinical picture of several conditions presenting movement disorders. Phenomenology and epidemiology of psychosis in Parkinson's disease have received wide attention; however, the presence of psychosis in other movement disorders is, comparatively, less well known.

Objectives

To review psychotic symptoms present in different movement disorders.

Methods

A comprehensive and structured literature search was performed to identify and analyze data on patients with movement disorders and comorbid psychosis.

Results

In monogenic parkinsonisms, such as PARK‐GBA, PARK‐LRRK2, and PARK‐SNCA, visual hallucinations related to dopamine replacement therapy are frequent as well as are delusions in PARK‐LRRK2 and PARK‐SNCA, but not in PARK‐GBA. Different types of delusions and hallucinations are found in Huntington's disease and other choreic disorders. In Tourette's syndrome, paranoid delusions as well as visual, olfactory, and auditory hallucinations have been described, which usually develop after an average of 10 years of disease. Delusions in ataxias are more frequent in ATX‐TBP, ATX‐ATN1, and ATX‐ATXN3, whereas it is rare in Friedreich's ataxia. Psychosis is also a prominent and frequent clinical feature in Fahr's disease, Wilson's disease, neurodegeneration with brain iron accumulation, and some lysosomal storage disorders, whereas it is uncommon in atypical parkinsonisms and dystonia. Psychosis usually occurs at late disease stages, but may appear as onset symptoms of the disease, especially in Wilson's disease, Huntington's disease, late‐onset Tays‐Sachs, and Niemann‐Pick.

Conclusion

Psychosis is a frequent comorbidity in most hyper‐ and hypokinetic movement disorders. Appropriate recognition is relevant both in the early and late disease stages.
Over the rainbow: A practical guide for fluorescent protein selection in plant FRET experiments
Authors: Denay Grégoire , Schultz Patrick , Hänsch Sebastian , Weidtkamp‐Peters Stefanie , Simon Rüdiger
Published: December 2019

Receptor‐like kinases (RLK) and receptor‐like proteins (RLP) often interact in a combinatorial manner depending on tissue identity, membrane domains, or endo‐ and exogenous cues, and the same RLKs or RLPs can generate different signaling outputs depending on the composition of the receptor complexes they are involved in. Investigation of their interaction partners in a spatial and dynamic way is therefore of prime interest to understand their functions. This is, however, limited by the technical complexity of assessing it in endogenous conditions. A solution to close this gap is to determine protein interaction directly in the relevant tissues at endogenous expression levels using Förster resonance energy transfer (FRET). The ideal fluorophore pair for FRET must, however, fulfil specific requirements: (a) The emission and excitation spectra of the donor and acceptor, respectively, must overlap; (b) they should not interfere with proper folding, activity, or localization of the fusion proteins; (c) they should be sufficiently photostable in plant cells. Furthermore, the donor must yield sufficient photon counts at near‐endogenous protein expression levels. Although many fluorescent proteins were reported to be suitable for FRET experiments, only a handful were already described for applications in plants. Herein, we compare a range of fluorophores, assess their usability to study RLK interactions by FRET‐based fluorescence lifetime imaging (FLIM) and explore their differences in FRET efficiency. Our analysis will help to select the optimal fluorophore pair for diverse FRET applications.
Structure of galactarate dehydratase, a new fold in an enolase involved in bacterial fitness after antibiotic treatment
Authors: Rosas‐Lemus Monica , Minasov George , Shuvalova Ludmilla , Wawrzak Zdzislaw , Kiryukhina Olga , Mih Nathan , Jaroszewski Lukasz , Palsson Bernhard , Godzik Adam , Satchell Karla J. F.
Published: December 2019

Galactarate dehydratase (GarD) is the first enzyme in the galactarate/glucarate pathway and catalyzes the dehydration of galactarate to 3‐keto‐5‐dehydroxygalactarate. This protein is known to increase colonization fitness of intestinal pathogens in antibiotic‐treated mice and to promote bacterial survival during stress. The galactarate/glucarate pathway is widespread in bacteria, but not in humans, and thus could be a target to develop new inhibitors for use in combination therapy to combat antibiotic resistance. The structure of almost all the enzymes of the galactarate/glucarate pathway were solved previously, except for GarD, for which only the structure of the N‐terminal domain was determined previously. Herein, we report the first crystal structure of full‐length GarD solved using a seleno‐methoionine derivative revealing a new protein fold. The protein consists of three domains, each presenting a novel twist as compared to their distant homologs. GarD in the crystal structure forms dimers and each monomer consists of three domains. The N‐terminal domain is comprised of a β‐clip fold, connected to the second domain by a long unstructured linker. The second domain serves as a dimerization interface between two monomers. The C‐terminal domain forms an unusual variant of a Rossmann fold with a crossover and is built around a seven‐stranded parallel β‐sheet supported by nine α‐helices. A metal binding site in the C‐terminal domain is occupied by Ca2+. The activity of GarD was corroborated by the production of 5‐keto‐4‐deoxy‐D‐glucarate under reducing conditions and in the presence of iron. Thus, GarD is an unusual enolase with a novel protein fold never previously seen in this class of enzymes.
Type I fatty acid synthase trapped in the octanoyl‐bound state
Authors: Rittner Alexander , Paithankar Karthik S. , Himmler Aaron , Grininger Martin
Published: December 2019

De novo fatty acid biosynthesis in humans is accomplished by a multidomain protein, the Type I fatty acid synthase (FAS). Although ubiquitously expressed in all tissues, fatty acid synthesis is not essential in normal healthy cells due to sufficient supply with fatty acids by the diet. However, FAS is overexpressed in cancer cells and correlates with tumor malignancy, which makes FAS an attractive selective therapeutic target in tumorigenesis. Herein, we present a crystal structure of the condensing part of murine FAS, highly homologous to human FAS, with octanoyl moieties covalently bound to the transferase (MAT—malonyl‐/acetyltransferase) and the condensation (KS—β‐ketoacyl synthase) domain. The MAT domain binds the octanoyl moiety in a novel (unique) conformation, which reflects the pronounced conformational dynamics of the substrate‐binding site responsible for the MAT substrate promiscuity. In contrast, the KS binding pocket just subtly adapts to the octanoyl moiety upon substrate binding. Besides the rigid domain structure, we found a positive cooperative effect in the substrate binding of the KS domain by a comprehensive enzyme kinetic study. These structural and mechanistic findings contribute significantly to our understanding of the mode of action of FAS and may guide future rational inhibitor designs.