bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Cardiac Mast Cell Maturation and Function by the Neurokinin-1 Receptor in the Fibrotic Heart
Authors: Widiapradja Alexander , Manteufel Edward J. , Dehlin Heather M. , Pena James , Goldspink Paul H. , Sharma Amit , Kolb Lauren L. , Imig John D. , Janicki Joseph S. , Lu Bao , Levick Scott P. 
Published: July 2019

AbstractCardiac fibrosis is an underlying cause of diastolic dysfunction, contributing to heart failure. Substance P (SP) activation of the neurokinin-1 receptor (NK-1R) contributes to cardiac fibrosis in hypertension. However, based on in vitro experiments, this does not appear to be via direct activation of cardiac fibroblasts. While numerous cells could mediate the fibrotic effects of SP, herein, we investigate mast cells (MC) as a mechanism mediating the fibrotic actions of SP, since MCs are known to play a role in cardiac fibrosis and respond to SP. Spontaneously hypertensive rats (SHR) were treated with the NK-1R antagonist L732138 (5 mg/kg/d) from 8 to 12 weeks of age. L732138 prevented increased MC maturation of resident immature MCs. NK-1R blockade also prevented increased cardiac MC maturation in angiotensin II-infused mice. MC-deficient mice were used to test the importance of MC NK-1Rs to MC activation. MC-deficient mice administered angiotensin II did not develop fibrosis; MC-deficient mice reconstituted with MCs did develop fibrosis. MC-deficient mice reconstituted with MCs lacking the NK-1R also developed fibrosis, indicating that NK-1Rs are not required for MC activation in this setting. In conclusion, the NK-1R causes MC maturation, however, other stimuli are required to activate MCs to cause fibrosis.
Golden Mutagenesis: An efficient multi-site-saturation mutagenesis approach by Golden Gate cloning with automated primer design
Authors: Püllmann Pascal , Ulpinnis Chris , Marillonnet Sylvestre , Gruetzner Ramona , Neumann Steffen , Weissenborn Martin J. 
Published: July 2019

AbstractSite-directed methods for the generation of genetic diversity are essential tools in the field of directed enzyme evolution. The Golden Gate cloning technique has been proven to be an efficient tool for a variety of cloning setups. The utilization of restriction enzymes which cut outside of their recognition domain allows the assembly of multiple gene fragments obtained by PCR amplification without altering the open reading frame of the reconstituted gene. We have developed a protocol, termed Golden Mutagenesis that allows the rapid, straightforward, reliable and inexpensive construction of mutagenesis libraries. One to five amino acid positions within a coding sequence could be altered simultaneously using a protocol which can be performed within one day. To facilitate the implementation of this technique, a software library and web application for automated primer design and for the graphical evaluation of the randomization success based on the sequencing results was developed. This allows facile primer design and application of Golden Mutagenesis also for laboratories, which are not specialized in molecular biology.
Automated detection and classification of early AMD biomarkers using deep learning
Authors: Saha Sajib , Nassisi Marco , Wang Mo , Lindenberg Sophiana , kanagasingam Yogi , Sadda Srinivas , Hu Zhihong Jewel 
Published: July 2019

AbstractAge-related macular degeneration (AMD) affects millions of people and is a leading cause of blindness throughout the world. Ideally, affected individuals would be identified at an early stage before late sequelae such as outer retinal atrophy or exudative neovascular membranes develop, which could produce irreversible visual loss. Early identification could allow patients to be staged and appropriate monitoring intervals to be established. Accurate staging of earlier AMD stages could also facilitate the development of new preventative therapeutics. However, accurate and precise staging of AMD, particularly using newer optical coherence tomography (OCT)-based biomarkers may be time-intensive and requires expert training which may not feasible in many circumstances, particularly in screening settings. In this work we develop deep learning method for automated detection and classification of early AMD OCT biomarker. Deep convolution neural networks (CNN) were explicitly trained for performing automated detection and classification of hyperreflective foci, hyporeflective foci within the drusen, and subretinal drusenoid deposits from OCT B-scans. Numerous experiments were conducted to evaluate the performance of several state-of-the-art CNNs and different transfer learning protocols on an image dataset containing approximately 20000 OCT B-scans from 153 patients. An overall accuracy of 87% for identifying the presence of early AMD biomarkers was achieved.
High concentration and yield production of mannose from açaí (Euterpe oleracea Mart.) seeds via mannanase-catalyzed hydrolysis
Authors: Monteiro Alvaro Ferreira , Miguez Ingrid Santos , Silva João Pedro R. Barros , Silva Ayla Sant’Ana da 
Published: July 2019

AbstractThe açaí seed corresponds to approximately 85% of the fruit’s weight and represents ~1.1 million metric tons of residue yearly accumulated in the Amazon region, resulting in an acute environmental and urban problem. To extract the highest value from this residue, this study aimed to evaluate its chemical composition to determine the appropriate applications and to develop conversion methods. First, mannan was confirmed as the major component of mature seeds, corresponding to 80% of the seed’s total carbohydrates and about 50% of its dry weight. To convert this high mannan content into mannose, a sequential process of dilute-acid and enzymatic hydrolysis was evaluated. Among different dilute-H2SO4hydrolysis conditions, 3%-acid for 60-min at 121 °C resulted in a 30% mannan hydrolysis yield and 41.7 g/L of mannose. Because ~70% mannan remained in the seed, a mannanase-catalyzed hydrolysis was sequentially performed with 2–20% seed concentration, reaching 146.3 g/L of mannose and a 96.8% yield with 20% solids. As far as we know, this is the highest reported concentration of mannose produced from a residue. Thus, this work provides fundamental data for achieving high concentrations and yields of mannose from açaí seeds, which could add commercial value to the seeds and improve the whole açaí productive chain.
Extensive post-transcriptional buffering of gene expression in the response to severe oxidative stress in baker’s yeast
Authors: Blevins William R. , Tavella Teresa , Moro Simone G. , Blasco-Moreno Bernat , Closa-Mosquera Adrià , Díez Juana , Carey Lucas B. , Albà M. Mar 
Published: July 2019

AbstractCells responds to diverse stimuli by changing the levels of specific effector proteins. These changes are usually examined using high throughput RNA sequencing data (RNA-Seq); transcriptional regulation is generally assumed to directly influence protein abundances. However, the correlation between RNA-Seq and proteomics data is in general quite limited owing to differences in protein stability and translational regulation. Here we perform RNA-Seq, ribosome profiling and proteomics analyses in baker’s yeast cells grown in rich media and oxidative stress conditions to examine gene expression regulation at various levels. With the exception of a small set of genes involved in the maintenance of the redox state, which are regulated at the transcriptional level, modulation of protein expression is largely driven by changes in the relative ribosome density across conditions. The majority of shifts in mRNA abundance are compensated by changes in the opposite direction in the number of translating ribosomes and are predicted to result in no net change at the protein level. We also identify a subset of mRNAs which is likely to undergo specific translational repression during stress and which includes cell cycle control genes. The study suggests that post-transcriptional buffering of gene expression may be more common than previously anticipated.
Phylogenetic and Developmental Constraints Dictate the Number of Cusps on Molars in Rodents
Authors: Burroughs Robert W. 
Published: July 2019

AbstractMammal tooth morphology and function correlate strongly with dietary ecology, and convergence is a major feature of mammalian tooth evolution. Yet, function and ecology are insufficient to explain morphological diversification and convergence within mammalian molar evolution; suggesting that development and phylogeny also limit possible structural solutions to selective pressures. Here, I usein silicomodels and empirical studies of extant and fossil rodent teeth to identify morphogenetic rules that influence molar morphology. Because rodents are the most diverse group of mammals with corresponding dental disparity they represent an excellent system for investigating how genetic interactions limit morphology. I find that lower first molars are limited to a minimum of four cusps and a maximum of nine cusps. Multiple developmental pathways produce the same numbers of cusps, despite highly variable cusp morphologies, indicating the existence of limits on how morphological evolution can fill a morphospace defined by cusp numbers. These constraints are both developmental and phylogenetic in nature and the identification of their influence on rodent molar shape provides a framework for investigation of how tooth batteries evolved an array of functions despite fundamental structural limits. The data presented here increase predictability of cusp number and evolutionary outcomes of rodent cheek dentition.
Alterations in Brain Structure and Amplitude of Low-frequency after 8 weeks of Mindfulness Meditation Training in Meditation-Naïve Subjects
Authors: Yang Chuan-Chih , Barrós-Loscertales Alfonso , Li Meng , Pinazo Daniel , Borchardt Viola , Ávila César , Walter Martin 
Published: July 2019

AbstractIncreasing neuroimaging evidence suggests that mindfulness meditation expertise is related to different functional and structural configurations of the default mode network (DMN), the salience network (SN) and the executive network at rest. However, longitudinal studies observing resting network plasticity effects in brains of novices who started to practice meditation are scarce and generally related to one dimension, such as structural or functional effects. The purpose of this study was to investigate structural and functional brain network changes (e.g. DMN) after 40 days of mindfulness meditation training in novices and set these in the context of potentially altered depression symptomatology and anxiety. We found overlapping structural and functional effects in precuneus, a posterior DMN region, where cortical thickness increased and low-frequency amplitudes (ALFF) decreased, while decreased ALFF in left precuneus/posterior cingulate cortex correlates with the reduction of (CES-D) depression scores. In conclusion, regional overlapping of structural and functional changes in precuneus may capture different components of the complex changes of mindfulness meditation training.
Male Red-crested Cardinal plumage coloration is associated with parental abilities and breeding performance
Authors: Segura Luciano N. , Mahler Bettina 
Published: July 2019

AbstractAvian plumage coloration deriving from carotenoid-based pigments is among the most honest signals of individual quality. It has been argued that females may differentially allocate resources based on mate attractiveness or quality, paying the costs of investing more in a current breeding attempt. We tested predictions of the differential allocation hypothesis on the natural variation of carotenoid-based plumage using the brightly red-colored head plumage of the Red-crested Cardinal (Paroaria coronata). It is to our knowledge the first time this hypothesis is tested on the natural variation of this pigment on a wild bird. We found that the brightness of the males’ red plumage patch is positively associated with their reproductive success and the nest defence they provide. We also found that brighter males invest less in their offspring (by delivering less food to their nestlings and poorly cleaning the nest) than duller males and, by contrast, females mated with brighter males invest more in parental care. Our results are consistent with the differential allocation hypothesis: differential allocation allowed breeding pairs with brighter males to produce more offspring, suggesting that it can be considered adaptive and should be included in studies of eco-evolutionary dynamics.
Differential Expression of Urinary Exosomal MicroRNAs miR-21-5p and miR-30b-5p in Individuals with Diabetic Kidney Disease
Authors: Zang Jinnan , Maxwell Alexander P. , Simpson David A. , McKay Gareth J. 
Published: July 2019

AbstractBiomarkers for the identification of diabetic kidney disease (DKD) are needed as current tests lack sensitivity for detecting early kidney damage. MicroRNAs (miRNAs) are short, non-coding regulatory ribonucleic acid (RNA) molecules commonly found in urinary exosomes differentially expressed as renal function declines. We evaluated urinary exosomal miRNA expression in persons with type 2 diabetes mellitus and DKD (T2DKD). 87 human urinary exosomal miRNAs were profiled in a discovery cohort of patients with T2DKD (n = 14) and age and gender matched controls with type 2 diabetes mellitus and normal renal function (T2DNRF; n = 15). Independent validation of differentially expressed target miRNAs was performed in a second cohort with T2DKD (n = 22) and two control groups: T2DNRF (n = 15) and controls with chronic kidney disease (CCKD) and poor renal function without diabetes (n = 18). In the discovery cohort, urinary miR-21-5p, let-7e-5p and miR-23b-3p were significantly upregulated in T2DKD compared to T2DNRF (p < 0.05). Conversely, miR-30b-5p and miR-125b-5p expression was significantly lower in T2DKD (p < 0.05). Independent validation confirmed up-regulation of miR-21-5p in the replication cohort in T2DKD (2.13-fold, p = 0.006) and in CCKD (1.73-fold, p = 0.024). In contrast, miR-30b-5p was downregulated in T2DKD (0.82-fold, p = 0.006) and in CCKD (0.66-fold, p < 0.002). This study identified differential expression of miR-21-5p and miR-30b-5p in individuals with diabetic kidney disease and poor renal function. These miRNAs represent potential biomarkers associated with the pathogenesis of renal dysfunction.
Genetic Risk for Rheumatoid Arthritis is Associated with Increased Striatal Volume in Healthy Young Adults
Authors: Avinun Reut , Nevo Adam , Hariri Ahmad R. 
Published: July 2019

AbstractRheumatoid arthritis (RA), an autoimmune disease, has recently been associated with increased striatal volume and decreased intracranial volume (ICV) in longstanding patients. As inflammation has been shown to precede the clinical diagnosis of RA and it is a known moderator of neuro- and gliogenesis, we were interested in testing whether these brain morphological changes appear before the clinical onset of disease in healthy young adult volunteers, as a function of relative genetic risk for RA. Genetic and structural MRI data were available for 516 healthy non-Hispanic Caucasian university students (275 women, mean age 19.78 ± 1.24 years). Polygenic risk scores were computed for each individual based on a genome-wide association study of RA, so that higher scores indicated higher risk. Striatal volume (sum of caudate, putamen, and nucleus accumbens volumes) and ICV were derived for each individual from high-resolution T1-weighted images. After controlling for sex, age, genetic components of ethnicity, socioeconomic status, and depressive symptoms, we found that higher RA polygenic risk scores were associated with increased striatal volume, but not decreased ICV. Our findings suggest that increased striatal volume may be linked to processes that precede disease onset, such as inflammation, while decreased ICV may relate to disease progression.
Nanotip-assisted photoreduction of silver nanostructures on chemically patterned ferroelectric crystals for surface enhanced Raman scattering
Authors: Wang Tzyy-Jiann , Chang Hsuan-Wei , Chen Ji-Sheng , Chiang Hai-Pang 
Published: July 2019

AbstractNanotips made of metal and semiconductor have been widely utilized in versatile applications to strengthen the electric field through lightning rod effect and localized surface plasmon resonance (LSPR) effect. Here, we present the utilization of ferroelectric nanotips to assist photoreduction of silver nanostructures for surface enhanced Raman scattering (SERS). Ferroelectric nanotips with spontaneous polarization posses the unique feature of producing the permanent electrostatic field without requiring external excitation, which differs from the present nanotips requiring electrical and optical excitation. The enhanced electrostatic field promotes the formation of silver nanoparticles by reducing the effect of Stern layer and accelerating the movement of photoelectrons and silver ions to the template surface. Experimental results show that sharp ferroelectric nanotips facilitate the formation of large-diameter nanoparticles with strong LSPR action. Compared to the conventional ferroelectric templates, the SERS substrates using nanotip-equipped ferroelectric templates produce 5.51 times larger Raman intensity, which can be further increased by >10.76 times by increasing the reaction time. The proposed SERS substrate owns the limit of detection <10−8 M and the enhancement factor of 2.3 × 109. The presented ferroelectric nanotips with permanent electrostatic field would open promising applications in the versatile areas, such as nanomaterial fabrication and optoelectronic devices.
Access to consciousness of briefly presented visual events is modulated by transcranial direct current stimulation of left dorsolateral prefrontal cortex
Authors: Sdoia Stefano , Conversi David , Pecchinenda Anna , Ferlazzo Fabio 
Published: July 2019

AbstractAdaptive behaviour requires the ability to process goal-relevant events at the expense of irrelevant ones. However, perception of a relevant visual event can transiently preclude access to consciousness of subsequent events — a phenomenon called attentional blink (AB). Here we investigated involvement of the left dorsolateral prefrontal cortex (DLPFC) in conscious access, by using transcranial direct current stimulation (tDCS) to potentiate or reduce neural excitability in the context of an AB task. In a sham-controlled experimental design, we applied between groups anodal or cathodal tDCS over the left DLPFC, and examined whether this stimulation modulated the proportion of stimuli that were consciously reported during the AB period. We found that tDCS over the left DLPFC affected the proportion of consciously perceived target stimuli. Moreover, anodal and cathodal tDCS had opposing effects, and exhibited different temporal patterns. Anodal stimulation attenuated the AB, enhancing conscious report earlier in the AB period. Cathodal stimulation accentuated the AB, reducing conscious report later in the AB period. These findings support the notion that the DLPFC plays a role in facilitating information transition from the unconscious to the conscious stage of processing.
A small molecule inhibitor of ER-to-cytosol protein dislocation exhibits anti-dengue and anti-Zika virus activity
Authors: Ruan Jingjing , Rothan Hussin A. , Zhong Yongwang , Yan Wenjing , Henderson Mark J. , Chen Feihu , Fang Shengyun 
Published: July 2019

AbstractInfection with flaviviruses, such as dengue virus (DENV) and the recently re-emerging Zika virus (ZIKV), represents an increasing global risk. Targeting essential host elements required for flavivirus replication represents an attractive approach for the discovery of antiviral agents. Previous studies have identified several components of the Hrd1 ubiquitin ligase-mediated endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, a cellular protein quality control process, as host factors crucial for DENV and ZIKV replication. Here, we report that CP26, a small molecule inhibitor of protein dislocation from the ER lumen to the cytosol, which is an essential step for ERAD, has broad-spectrum anti-flavivirus activity. CP26 targets the Hrd1 complex, inhibits ERAD, and induces ER stress. Ricin and cholera toxins are known to hijack the protein dislocation machinery to reach the cytosol, where they exert their cytotoxic effects. CP26 selectively inhibits the activity of cholera toxin but not that of ricin. CP26 exhibits a significant inhibitory activity against both DENV and ZIKV, providing substantial protection to the host cells against virus-induced cell death. This study identified a novel dislocation inhibitor, CP26, that shows potent anti-DENV and anti-ZIKV activity in cells. Furthermore, this study provides the first example of the targeting of host ER dislocation with small molecules to combat flavivirus infection.
Treatment of splenic flexure colon cancer: a comparison of three different surgical procedures: Experience of a high volume cancer center
Authors: Rega Daniela , Pace Ugo , Scala Dario , Chiodini Paolo , Granata Vincenza , Fares Bucci Andrea , Pecori Biagio , Delrio Paolo 
Published: July 2019

AbstractExtended right or left hemicolectomy are the most common surgical treatments for splenic flexure colon cancer. Extended resection (including distal pancreasectomy and/or splenectomy), has been often indicated for the treatment for the splenic flexure cancer, because the lymphatic drainage at this site is poorly defined and assumed as heterogeneous. Between January 2006 and May 2016, 103 patients with splenic flexure colon cancer were enrolled in the study. We evaluated the clinicopathological findings and outcomes of all patients and associated them to the different surgical treatment. Out of 103 selected cases an extended right hemicolectomy was performed in 22 (21.4%) patients, an extended left hemicolectomy in 24 (23.3%) patients, a segmental resection of the splenic flexure in 57 (55.3%) patients; the combined resection of adjacent organs showing tumor adherence was carried out in 11 (10.7%) patients. The tumor infiltrated near organs (T4) in 5 patients. No significant differences in complications were found among the three groups. In all groups no differences were found in the total number of harvested lymphnodes. After a median follow-up of 42 months, 30 recurrences and 19 deaths occurred (12 for tumor progression). There was no difference in overall and progression free survival among the three different surgical treatments. According to our results, the partial resection of splenic flexure was not associated with a worse prognosis and it was leading for a satisfactory oncological outcome. It is our opinion that the extended surgery is seldomly indicated to cure splenic flexure cancer.
Effect of Charge accumulation on Magnetic Rayleigh-Taylor Instability
Authors: Liu Kangkang 
Published: July 2019

AbstractThe intuitive physical description of magnetic Rayleigh-Taylor instability in some textbooks is generally considered to be: a small perturbation causes current discontinuity, which produce charge accumulation, the electric field produced by the accumulated charge amplify the initial perturbation. However, in calculating the linear growth rate of magnetic Rayleigh-Taylor instability (MRTI), the displacement current term in the Maxwell’s equations is ignored, which means the contribution of charge accumulation to the growth of MRTI is totally ignored. In this article, we calculated the linear growth rate of MRTI with the displacement current term in Maxwell’s equations retained. We show that the contribution of charge accumulation to the growth of MRTI is negligible only when the nominal Alfvén speed is much smaller than the light speed. For space plasma whose nominal Alfvén speed is generally much smaller than the light speed, the linear growth rate previous calculated is right but the intuitive physical description of MRTI is wrong. For laboratory plasma whose nominal Alfvén speed maybe comparable to light speed, the intuitive physical description of MRTI is also inaccurate and the linear growth rate of MRTI is undervalued.