bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-intensity vibration restores nuclear YAP levels and acute YAP nuclear shuttling in mesenchymal stem cells subjected to simulated microgravity
Authors: Thompson Matthew , Woods Kali , Newberg Joshua , Oxford Julia Thom , Uzer Gunes 
Published: December 2020

AbstractReducing the musculoskeletal deterioration that astronauts experience in microgravity requires countermeasures that can improve the effectiveness of otherwise rigorous and time-expensive exercise regimens in space. The ability of low-intensity vibrations (LIV) to activate force-responsive signaling pathways in cells suggests LIV as a potential countermeasure to improve cell responsiveness to subsequent mechanical challenge. Mechanoresponse of mesenchymal stem cells (MSC), which maintain bone-making osteoblasts, is in part controlled by the “mechanotransducer” protein YAP (Yes-associated protein), which is shuttled into the nucleus in response to cyto-mechanical forces. Here, using YAP nuclear shuttling as a measurement outcome, we tested the effect of 72 h of clinostat-induced simulated microgravity (SMG) and daily LIV application (LIVDT) on the YAP nuclear entry driven by either acute LIV (LIVAT) or Lysophosphohaditic acid (LPA), applied after the 72 h period. We hypothesized that SMG-induced impairment of acute YAP nuclear entry would be alleviated by the daily application of LIVDT. Results showed that while both acute LIVAT and LPA treatments increased nuclear YAP entry by 50 and 87% over the basal levels in SMG-treated MSCs, nuclear YAP levels of all SMG groups were significantly lower than non-SMG controls. LIVDT, applied in parallel to SMG, restored the SMG-driven decrease in basal nuclear YAP to control levels as well as increased the LPA-induced but not LIVAT-induced YAP nuclear entry over SMG only, counterparts. These cell-level observations suggest that daily LIV treatments are a feasible countermeasure for restoring basal nuclear YAP levels and increasing the YAP nuclear shuttling in MSCs under SMG.
Targeting the coronavirus SARS-CoV-2: computational insights into the mechanism of action of the protease inhibitors lopinavir, ritonavir and nelfinavir
Authors: Bolcato Giovanni , Bissaro Maicol , Pavan Matteo , Sturlese Mattia , Moro Stefano 
Published: December 2020

AbstractCoronavirus SARS-CoV-2 is a recently discovered single-stranded RNA betacoronavirus, responsible for a severe respiratory disease known as coronavirus disease 2019, which is rapidly spreading. Chinese health authorities, as a response to the lack of an effective therapeutic strategy, started to investigate the use of lopinavir and ritonavir, previously optimized for the treatment and prevention of HIV/AIDS viral infection. Despite the clinical use of these two drugs, no information regarding their possible mechanism of action at the molecular level is still known for SARS-CoV-2. Very recently, the crystallographic structure of the SARS-CoV-2 main protease (Mpro), also known as C30 Endopeptidase, was published. Starting from this essential structural information, in the present work we have exploited supervised molecular dynamics, an emerging computational technique that allows investigating at an atomic level the recognition process of a ligand from its unbound to the final bound state. In this research, we provided molecular insight on the whole recognition pathway of Lopinavir, Ritonavir, and Nelfinavir, three potential C30 Endopeptidase inhibitors, with the last one taken into consideration due to the promising in-vitro activity shown against the structurally related SARS-CoV protease.
Behavioural and cognitive mechanisms of Developmental Topographical Disorientation
Authors: Burles Ford , Iaria Giuseppe 
Published: December 2020

AbstractIndividuals affected by Developmental Topographical Disorientation (DTD) get lost on a daily basis, even in the most familiar of surroundings such as their neighbourhood, the building where they have worked for many years, and, in extreme cases, even in their own homes. Individuals with DTD report a lifelong selective inability to orient despite otherwise well-preserved general cognitive functions, and the absence of any acquired brain injury or neurological condition, with general intelligence reported to be within the normal range. To date, the mechanisms underlying such a selective developmental condition remain unknown. Here, we report the findings of a 10-year-long study investigating the behavioural and cognitive mechanisms of DTD in a large sample of 1211 cases. We describe the demographics, heritability pattern, self-reported and objective spatial abilities, and some personality traits of individuals with DTD as compared to a sample of 1624 healthy controls; importantly, we test the specific hypothesis that the presence of DTD is significantly related to the inability of the individuals to form a mental representation of the spatial surroundings (i.e., a cognitive map). We found that individuals with DTD reported relatively greater levels of neuroticism and negative affect, and rated themselves more poorly on self-report measures of memory and imagery skills related to objects, faces, and places. While performing interactive tasks, as a group, the individuals with DTD performed slightly worse on a scene-based perspective-taking task, and, notably struggled to solve tasks that demand the generation and use of a cognitive map. These novel findings help define the phenotype of DTD, and lay the foundation for future studies of the neurological and genetic mechanisms of this lifelong condition.
Particle-in-cell simulation of the effect of dust charge fluctuation on ion acoustic waves in a dusty plasma
Authors: Changmai Suniti , Bora Madhurjya P. 
Published: December 2020

AbstractA new hybrid-particle-in-cell (PIC)-Monte Carlo Collision (h-PIC-MCC) algorithm is presented here. The code correctly simulates the damping of ion acoustic wave due to dust charge fluctuation in a dusty plasma along with other kinetic effects such as Landau damping. In the model, on event of a collision between a charged particle and a dust particle, a randomised probability determines whether the charged particle is absorbed by the dust with the collision cross section being determined dynamically by the overall interaction scenario. We find that this method is versatile enough as it can also include the size and mass distribution for the dust particles, in addition to the charged species dynamics. As such, it can be adopted to study numerous phenomena that occur in diverse dusty plasma environments. We believe that the damping of the ion acoustic wave through dust charge fluctuation is being demonstrated, for the first time, with a PIC code, in this work.
Network and pathway expansion of genetic disease associations identifies successful drug targets
Authors: MacNamara Aidan , Nakic Nikolina , Amin Al Olama Ali , Guo Cong , Sieber Karsten B. , Hurle Mark R. , Gutteridge Alex 
Published: December 2020

AbstractGenetic evidence of disease association has often been used as a basis for selecting of drug targets for complex common diseases. Likewise, the propagation of genetic evidence through gene or protein interaction networks has been shown to accurately infer novel disease associations at genes for which no direct genetic evidence can be observed. However, an empirical test of the utility of combining these approaches for drug discovery has been lacking. In this study, we examine genetic associations arising from an analysis of 648 UK Biobank GWAS and evaluate whether targets identified as proxies of direct genetic hits are enriched for successful drug targets, as measured by historical clinical trial data. We find that protein networks formed from specific functional linkages such as protein complexes and ligand–receptor pairs are suitable for even naïve guilt-by-association network propagation approaches. In addition, more sophisticated approaches applied to global protein–protein interaction networks and pathway databases, also successfully retrieve targets enriched for clinically successful drug targets. We conclude that network propagation of genetic evidence can be used for drug target identification.
Comparison of extraocular and intraocular pressure transducers for measurement of transient intraocular pressure fluctuations using continuous wireless telemetry
Authors: Jasien Jessica V. , Zohner Ye Emma , Asif Sonia Kuhn , Rhodes Lindsay A. , Samuels Brian C. , Girkin Christopher A. , Morris Jeffrey S. , Downs J. Crawford 
Published: December 2020

AbstractThe optimal approach for continuous measurement of intraocular pressure (IOP), including pressure transducer location and measurement frequency, is currently unknown. This study assessed the capability of extraocular (EO) and intraocular (IO) pressure transducers, using different IOP sampling rates and duty cycles, to characterize IOP dynamics. Transient IOP fluctuations were measured and quantified in 7 eyes of 4 male rhesus macaques (NHPs) using the Konigsberg EO system (continuous at 500 Hz), 12 eyes of 8 NHPs with the Stellar EO system and 16 eyes of 12 NHPs with the Stellar IO system (both measure at 200 Hz for 15 s of every 150 s period). IOP transducers were calibrated bi-weekly via anterior chamber manometry. Linear mixed effects models assessed the differences in the hourly transient IOP impulse, and transient IOP fluctuation frequency and magnitude between systems and transducer placements (EO versus IO). All systems measured 8000–12,000 and 5000–6500 transient IOP fluctuations per hour > 0.6 mmHg, representing 8–16% and 4–8% of the total IOP energy the eye must withstand during waking and sleeping hours, respectively. Differences between sampling frequency/duty cycle and transducer placement were statistically significant (p < 0.05) but the effect sizes were small and clinically insignificant. IOP dynamics can be accurately captured by sampling IOP at 200 Hz on a 10% duty cycle using either IO or EO transducers.
Hyperoxia in portal vein causes enhanced vasoconstriction in arterial vascular bed
Authors: Eshmuminov Dilmurodjon , Becker Dustin , Hefti Max L. , Mueller Matteo , Hagedorn Catherine , Dutkowski Philipp , Rudolf von Rohr Philipp , Halbe Maximilian , Segerer Stephan , Tibbitt Mark W. , Bautista Borrego Lucia , Schuler Martin J. , Clavien Pierre-Alain 
Published: December 2020

AbstractLong-term perfusion of liver grafts outside of the body may enable repair of poor-quality livers that are currently declined for transplantation, mitigating the global shortage of donor livers. In current ex vivo liver perfusion protocols, hyperoxic blood (arterial blood) is commonly delivered in the portal vein (PV). We perfused porcine livers for one week and investigated the effect of and mechanisms behind hyperoxia in the PV on hepatic arterial resistance. Applying PV hyperoxia in porcine livers (n = 5, arterial PV group), we observed an increased need for vasodilator Nitroprussiat (285 ± 162 ml/week) to maintain the reference hepatic artery flow of 0.25 l/min during ex vivo perfusion. With physiologic oxygenation (venous blood) in the PV the need for vasodilator could be reduced to 41 ± 34 ml/week (p = 0.011; n = 5, venous PV group). This phenomenon has not been reported previously, owing to the fact that such experiments are not feasible practically in vivo. We investigated the mechanism of the variation in HA resistance in response to blood oxygen saturation with a focus on the release of vasoactive substances, such as Endothelin 1 (ET-1) and nitric oxide (NO), at the protein and mRNA levels. However, no difference was found between groups for ET-1 and NO release. We propose direct oxygen sensing of endothelial cells and/or increased NO break down rate with hyperoxia as possible explanations for enhanced HA resistance.
Experiments to understand crystallization of levitated high temperature silicate melt droplets under low vacuum conditions
Authors: Mishra Biswajit , Manvar Pratikkumar , Choudhury Kaushik , Karagadde S. , Srivastava Atul 
Published: December 2020

AbstractWe report experiments on crystallization of highly undercooled forsterite melt droplets under atmospheric and sub-atmospheric pressure conditions. Experiments have been conducted under non-contact conditions using the principles of aero-dynamic levitation. Real time dynamics of solidification, along with the transient evolution of surface textures, have been recorded using high speed camera for three cooling rates. These images have been matched with the time-tagged temperature data to understand the effect of pressure conditions and cooling rates on the crystallization dynamics. Compared to normal pressure, relatively higher levels of undercooling could be achieved under sub-atmospheric conditions. Results showed a strong dependence of surface textures on pressure conditions. For any externally employed cooling rate, relatively small length scale morphological textures were observed under sub-atmospheric conditions, in comparison to those achieved under ambient conditions. The observed trends have been explained on the basis of influence of pressure conditions on recalescence phenomenon and the rate at which latent heat of crystallization gets dissipated from the volume of the molten droplet. Sub-atmospheric experiments have also been performed to reproduce one of the classical chondrule textures, namely the rim + dendrite double structure. Possible formation conditions of this double structure have been discussed vis-à-vis those reported in the limited literature. To the best of our knowledge, the reported study is one of the first attempts to reproduce chondrules-like textures from highly undercooled forsterite melt droplets under sub-atmospheric non-contact conditions.
Effects of Capsicum annuum supplementation on the components of metabolic syndrome: a systematic review and meta-analysis
Authors: Jang Hwan-Hee , Lee Jounghee , Lee Sung-Hyen , Lee Young-Min 
Published: December 2020

AbstractMetabolic syndrome (MetS) has increasingly gained importance as the main risk factor for cardiovascular diseases and type II diabetes mellitus. Various natural compounds derived from plants are associated with beneficial effects on the incidence and progression of MetS. This study aimed to evaluate the effects of Capsicum annuum on factors related to MetS by assessing randomized controlled trials (written in English). We searched the online databases of PubMed, Embase, Google scholar, and Cochrane Library up to April 2020. ‘Patient/Population, Intervention, Comparison and Outcomes’ format was used to determine whether intervention with C. annuum supplementation compared with placebo supplementation had any effect on the components of MetS among participants. We considered standardized mean differences (SMD) with 95% confidence intervals (CI) as effect size measures using random-effects model. Analysis of the included 11 studies (n = 609) showed that C. annuum supplementation had significant effect on low density lipoprotein-cholesterol [SMD = − 0.39; 95% CI − 0.72, − 0.07; P = 0.02; prediction interval, − 1.28 to 0.50] and marginally significant effect on body weight [SMD = − 0.19; 95% CI − 0.40, 0.03; P = 0.09]. However, larger and well-designed clinical trials are needed to investigate the effects of C. annuum on MetS.
Genotype selection for phytochemical content and pharmacological activities in ethanol extracts of fifteen types of Orthosiphon aristatus (Blume) Miq. leaves using chemometric analysis
Authors: Batubara Irmanida , Komariah Komariah , Sandrawati Apong , Nurcholis Waras 
Published: December 2020

AbstractOrthosiphon aristatus (Blume) Miq. of the Lamiaceae family, called as kumis kucing in Indonesia, is a valuable medicinal plant for their pharmacological properties. The present study comprised of fifteen genotypes of O. aristatus was undertaken to evaluate the genotypes based on phytochemical content and pharmacological activities of leaves ethanol extract. Chemometric analysis (correlation and principal component analysis) was also used to investigate the genetic variability based on phytochemical content and pharmacological activities of O. aristatus genotypes. Results of phytochemical characterization showed that total phenolic ranged from 1.48 to 36.08 (maximum in A15) mg GAE/g DW, total flavonoid ranged from 0.10 to 3.07 (maximum in A15) mg QE/g DW, sinensetin ranged from 0.36 to 4.02 (maximum in A11) mg/g DW, and rosmarinic acid ranged 0.06 to 7.25 (maximum in A7) mg/g DW. Antioxidant activity was tested using DPPH and FRAP assay. Antioxidant results showed that DPPH ranged from 1.68 to 15.55 (maximum in A15) μmol TE/g DW and FRAP ranged from 0.07 to 1.60 (maximum in A1 and A7) μmol TE/g DW. The genotype A8 showed the highest cytotoxic activities against HeLa (66.25%) and MCF-7 (61.79%) cell lines. Maximum α-glucosidase inhibitory activity was recorded in genotype A2 with the value of 62.84%. The genotypes A1, A2, A7, A11, and A15 were identified as superior based on their phytochemicals content and pharmacological activities coupled with chemometric analysis. This finding is important for breeding studies and also the pharmaceutical perspective of O. aristatus.
Management des pulmonalen Rundherdes
Authors: Schaefer-Prokop Cornelia 
Published: December 2020

ZusammenfassungPulmonale Rundherde sind fokale rundliche Lungenparenchymverdichtungen, die über 3 mm und unter 3 cm groß sind. Sie haben je nach ihrer Größe, Form, Dichte und Lage, aber auch je nach Komorbidität und Alter des Patienten eine unterschiedliche Bedeutung. Dieser Beitrag beschreibt ihre Diagnostik und die ggf. notwendigen Kontrolluntersuchungen.
The Impact of Narrow-band Imaging on the Pre- and Intra- operative Assessments of Neoplastic and Preneoplastic Laryngeal Lesions. A Systematic Review
Authors: Saraniti Carmelo , Chianetta Enzo , Greco Giuseppe , Mat Lazim Norhafiza , Verro Barbara 
Published: December 2020

Introduction Narrow-band imaging is an endoscopic diagnostic tool that, focusing on superficial vascular changes, is useful to detect suspicious laryngeal lesions, enabling their complete excision with safe and tailored resection margins.
Objectives To analyze the applications and benefits of narrow-band imaging in detecting premalignant and malignant laryngeal lesions through a comparison with white-light endoscopy.
Data Synthesis A literature search was performed in the PubMed, Scopus and Web of Science databases using strict keywords. Then, two authors independently analyzed the articles, read the titles and abstracts, and read completely only the relevant studies according to certain eligibility criteria. In total, 14 articles have been included in the present review; the sensitivity, specificity, positive and negative predictive values, and accuracy of pre- and/or intraoperative narrow-band imaging were analyzed. The analysis showed that narrow-band imaging is better than white-light endoscopy in terms of sensitivity, specificity, positive and negative predictive values, and accuracy regarding the ability to identify cancer and/or precancerous laryngeal lesions. Moreover, the intraoperative performance of narrow-band imaging resulted more effective than the in-office performance.
Conclusion Narrow-band imaging is an effective diagnostic tool to detect premalignant and malignant laryngeal lesions and to define proper resection margins. Moreover, narrow-band imaging is useful in cases of leukoplakia that may cover a possible malignant lesion and that cannot be easily assessed with white-light endoscopy. Finally, a shared, simple and practical classification of laryngeal lesions, such as that of the European Laryngological Society, is required to identify a shared lesion management strategy.
Key Points
A bacterial cytolinker couples positioning of magnetic organelles to cell shape control
Authors: Pfeiffer Daniel , Toro-Nahuelpan Mauricio , Awal Ram Prasad , Müller Frank-Dietrich , Bramkamp Marc , Plitzko Jürgen M. , Schüler Dirk 
Published: December 2020

Significance
The bacterial cytoskeleton is an intricate meshwork of filaments, fundamental for cell shape determination and subcellular organization. An elaborate example is found in magnetotactic bacteria, which employ a distinct cytoskeleton, the “magnetoskeleton,” to align magnetic nanoparticles (magnetosomes) for navigation within the geomagnetic field. Thus far, cytoskeletal determinants for cell shape in magnetotactic bacteria, and whether those are functionally linked to the magnetoskeleton, has remained unknown. Here, we describe the structural protein CcfM (curvature-inducing coiled-coil filament interacting with the magnetoskeleton), which functions as an interconnector (cytolinker) between the magnetoskeleton and cytoskeleton. CcfM not only controls cell curvature, but also formation of coherent cell-spanning magnetosome chains, enhancing magnetic navigation within environmental habitats.
Cellular proteostasis decline in human senescence
Authors: Sabath Niv , Levy-Adam Flonia , Younis Amal , Rozales Kinneret , Meller Anatoly , Hadar Shani , Soueid-Baumgarten Sharon , Shalgi Reut 
Published: December 2020

Significance
Protein homeostasis (proteostasis), the balance between protein synthesis, folding, and degradation, is thought to deteriorate with age, and the prevalence of protein misfolding diseases (e.g., Alzheimer’s, Parkinson’s, etc.) with human aging is increased. However, while in worms this phenomenon has been well established, in humans, it remained unclear. Here, we show that proteostasis is declined in human cellular aging, termed cellular senescence. We found that while stress sensing is enhanced in senescent cells, and their response at the level of protein synthesis is intact, they fail to properly activate multiple programs required for stress adaptation at the level of gene transcription. Our findings support the notion that proteostasis decline may have major implications on human aging.
On three-dimensional rotating polymeric fiber jets with gravity effect
Authors: Riahi D N 
Published: December 2020

Abstract
We consider rotationally driven three-dimensional nonlinear polymeric fiber jets with the effect of gravity force. We implement an empirical viscosity model for the polymeric fluid of such flows to investigate the properties of the three-dimensional polymeric fiber jets generated by the imposed rotational forces. We apply theoretical and numerical techniques to determine the expressions for the leading order nonlinear solutions for the jet quantities such as radius, speed, stretching rate, strain rate and jet centerline versus arc length, and we calculate these quantities for different values of the parameters that represent the effects due to gravity, rotation, viscosity, surface tension and relaxation time. We find, in particular, that three-dimensionality of the jet system and the presence of the gravity force on the curved polymeric fiber jet can be significant in the sense that the values of the jet speed, strain rate, stretching rate and the centerline curvature are notably raised up and the jet radius size is notably dropped down and more so with increasing the arc length and the parameters due to gravity, rotation and the relaxation time of the polymeric jet.