bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic dietary erythritol exposure elevates fasting plasma erythritol levels but does not cause weight gain or modify glucose homeostasis in mice
Authors: Ortiz Semira R. , Field Martha S.
Published: January 2021

Objective

Erythritol is both a common non-nutritive sweetener (NNS) and an endogenous product of glucose metabolism. Recent reports indicate that elevated plasma erythritol is a predictive biomarker of cardiometabolic disease onset and complications. Although short-term erythritol consumption has been evaluated, the effect of chronically elevated circulating erythritol on adiposity and glucose metabolism has not. This study investigated the effect of longer-term erythritol consumption on weight gain and glucose tolerance, and the interaction between dietary composition and erythritol supplementation on these parameters.

Methods

8-week-old and 20-week-old C57BL/6J mice were randomized to consume low-fat diet (LFD), high-fat diet (HFD), LFD with 40g/kg erythritol (LFD+ERY), and HFD with 40g/kg erythritol (HFD+ERY) groups. After 8 weeks, plasma erythritol, body weight and composition, food intake, glucose tolerance, and brown adipose tissue (BAT) uncoupling protein 1 (UCP1) expression were measured.

Results

Plasma erythritol was elevated 40-fold in mice consuming LFD+ERY or HFD+ERY relative to mice consuming LFD or HFD, respectively. Liver and kidney tissue contained higher levels of erythritol than adipose. Unexpectedly, there was no effect of erythritol supplementation on body weight or glucose tolerance in 8- or 20-week-old mice fed LFD+ERY, or in 8-week-old mice fed HFD+ERY. In 20-week-old mice fed HFD+ERY, there was a significant interaction between erythritol and body weight (p<0.0001) compared to controls, but the main effect of diet was not significant. We also found no effect of chronic erythritol consumption on BAT UCP1 expression.

Conclusion

Prolonged erythritol consumption did not significantly impact body weight, composition, or glucose tolerance. This suggests that dietary erythritol does not contribute to the development of cardiometabolic disease.
Protoporphyrin-IX nanostructures modulate their protein aggregation ability via differential oxidation and protein binding
Authors: Maitra Dhiman , Pinsky Benjamin M. , Soherawardy Amenah , Zheng Haiyan , Banerjee Ruma , Omary M. Bishr
Published: January 2021

Porphyrias are caused by genetic defects in the heme biosynthetic pathway and are associated with accumulation of high levels of porphyrins that become cytotoxic. Porphyrins, due to their amphipathic nature, spontaneously associate into different nanostructures but very little is known about the effect of porphyrin speciation on the cytotoxic effects of porphyrins. Previously we demonstrated the unique ability of fluorescent biological porphyrins, including protoporphyrin IX (PP-IX), to cause organelle selective protein aggregation, which we posit to be a major mechanism by which porphyrins exerts their cytotoxic effect. Herein, we tested the hypothesis that PP-IX-mediated protein aggregation is modulated by different PP-IX nanostructures via a mechanism that depends on their oxidizing potential and protein binding ability. We demonstrate that PP-IX nanostructure formation is reversible in nature, and that nanostructure size modulates consequent protein oxidation and aggregation potential. We also show that albumin, the most abundant serum protein, preferentially binds PP-IX dimers and enhances their oxidizing ability. Additionally, extracellular albumin protects from intracellular porphyrinogenic stress and protein aggregation by acting as a PP-IX sponge. This work highlights the importance of PP-IX speciation in the context of the porphyrias, and offers insights into potential novel therapeutic approaches.
Unfolding the Apoptotic Mechanism of Antioxidant Enriched-Leaves ofTabebuia pallidain EAC Cells
Authors: Rahman Md. Mahbubur , Khan Muhammad Ali , Reza A. S. M. Ali , Sujon Khaled Mahmud , Sharmin Rokshana , Rashid Mamunur , Sadik Md. Golam , Reza Md. Abu , Tsukahara Toshifumi , Mosaddik Ashik , Gobe Glenda C , Alam AHM Khurshid
Published: January 2021

Targeting apoptosis is a promising approach to inhibit the abnormal cell proliferation of cancer progression. Existing anti-apoptotic drugs, many derived from chemical substances, have often failed to combat cancer development and progression. Therefore, identification of apoptosis-inducing anticancer agents from plant-derived sources has become a key aim in cancer research. The present study was designed to explore the regulation of apoptosis byTabebuia pallida(T. pallida) using an Ehrlich Ascites Carcinoma (EAC) mouse model and compositional analysis by LC-ESI-MS/MS. Dried and powderedT. pallidaleaves (TPL), stem bark (TPSB), root bark (TPRB) and flowers (TPF) were extracted with 80% methanol. Using cultured EAC cells and EAC-bearing mice with and without these extracts, anticancer activities were studied by assessing cytotoxicity and tumor cell growth inhibition, changes in life span of mice, and hematological and biochemical parameters. Apoptosis was analyzed by microscopy and expression of selected apoptosis-related genes (Bcl-2, Bcl-xL, NFκ-B, PARP-1, p53, Bax, caspase-3 and -8) using RT-PCR. LC-ESI-MS analysis was performed to identify the major compounds from the most active extracts. In EAC mice compared with untreated controls, the TPL extract exhibited the highest cytotoxicity with significant tumor cell growth inhibition (p< 0.001), reduced ascites by body weight (p< 0.01), increased the life span (p<0.001), normalized blood parameters (RBC/WBC counts), and increased the levels of superoxide dismutase and catalase. TPL-treated EAC cells showed apoptotic characteristics of membrane blebbing, chromatin condensation and nuclear fragmentation, and caspase-3 activation, compared with untreated EAC cells. Moreover, annexin V-FITC and propidium iodide signals were greatly enhanced in response to TPL treatment, indicating apoptosis induction. Pro- and anti-apoptotic signaling after TPL treatment demonstrated up-regulated p53, Bax and PARP-1, and down-regulated NFκ-B, Bcl-2 and Bcl-xL expression, suggesting that TPL shifts the balance of pro- and anti-apoptotic genes towards cell death. LC-ESI-MS data of TPL showed a mixture of glycosides, lapachol, and quercetin antioxidant and its derivatives that were significantly linked to cancer cell targets. In conclusion, the TPL extract ofT. pallidapossesses significant anticancer activity. The tumor suppressive mechanism is due to apoptosis induced by activation of antioxidant enzymes and caspases and mediated by a change in the balance of pro- and anti-apoptotic genes that promotes cell death.

Graphical Abstract
Quantitative dissection of color patterning in the foliar ornamental Coleus reveals underlying features driving aesthetic value
Authors: Li Mao , Coneva Viktoriya , Clark David , Chitwood Dan , Frank Margaret
Published: January 2021

Coleus is a popular ornamental plant that exhibits a diverse array of foliar color patterns. New cultivars are currently hand selected by both amateur and experienced plant breeders. In this study, we reimagine coleus breeding using a quantitative color analysis framework.

Despite impressive advances in high-throughput data collection and processing, complex color patterns remain challenging to extract from image datasets. Using a new phenotyping approach called “ColourQuant,” we extract and analyze pigmentation patterns from one of the largest coleus breeding populations in the world.

Working with this massive dataset, we are able to analyze quantitative relationships between maternal plants and their progeny, identify features that underlie breeder-selections, and collect and compare consumer input on trait preferences.

This study is one of the most comprehensive explorations into complex color patterning in plant biology and provides new insights and tools for exploring the color pallet of the plant kingdom.
Cortical responses to vagus nerve stimulation are modulated by brain state in non-human primates
Authors: Rembado Irene , Song Weiguo , Su David K. , Levari Ariel , Shupe Larry E. , Perlmutter Steve , Fetz Eberhard , Zanos Stavros
Published: January 2021

Vagus nerve stimulation (VNS) has been tested as therapy for several brain disorders and as a means to modulate cortical excitability and brain plasticity. Cortical effects of VNS, manifesting as vagal-evoked potentials (VEPs), are thought to arise from activation of ascending cholinergic and noradrenergic systems. However, it is unknown whether those effects are modulated by brain state at the time of stimulation. In 2 freely behaving macaque monkeys, we delivered trains of left cervical VNS at different frequencies (5-300 Hz) while recording local field potentials (LFPs) from sites in contralateral prefrontal, sensorimotor and parietal cortical areas. Brain states were inferred from spectral components of LFPs and the presence of overt movement: active awake, resting awake, REM sleep and NREM sleep. VNS elicited VEPs comprising early (<70 ms), intermediate (70-250 ms) and late (>250 ms) components in all sampled cortical areas. The magnitude of only the intermediate and late components was modulated by brain state and pulsing frequency. These findings have implications for the role of ongoing cortical activity and brain state in shaping cortical responses to peripheral stimuli, for the modulation of vagal interoceptive signaling by cortical states, and for the calibration of VNS therapies.
Single Cell Enhancer Activity Maps Neuronal Lineages in Embryonic Mouse Basal Ganglia
Authors: Su-Feher Linda , Rubin Anna N. , Silberberg Shanni N. , Catta-Preta Rinaldo , Lim Kenneth J. , Zdilar Iva , McGinnis Christopher S. , McKinsey Gabriel L. , Rubino Thomas E. , Hawrylycz Michael , Thompson Carol , Gartner Zev J. , Puelles Luis , Zeng Hongkui , Rubenstein John L. R. , Nord Alex S.
Published: January 2021

Enhancers integrate transcription factor signaling pathways that drive cell fate specification in the developing brain. We used single cell RNA-sequencing (scRNA-seq) to capture enhancer activity at single cell resolution and delineate specification of cells labeled by enhancers in mouse medial, lateral, and caudal ganglionic eminences (MGE, LGE, and CGE) at embryonic day (E)11.5. We combine enhancer-based reporter labeling with single-cell transcriptional readout to characterize enhancer activity and define cell populations in vivo. Seven enhancers had diverse activities in specific progenitor and neuronal populations within the GEs. We then applied enhancer-based labeling, scRNA-seq, and analysis of in situ hybridization (ISH) data to distinguish subtypes of MGE-derived GABAergic and cholinergic projection neurons and interneurons. This work demonstrates how the power of scRNA-seq can be extended by enhancer-based labelling and leveraging ISH data and reveals novel lineage specification paths underlying patterning of developing mouse brain.
An SR protein is essential for the recovery of malaria parasites from DNA damage and exposure to artemisinin
Authors: Singh Brajesh Kumar , Goyal Manish , Simantov Karina , Kaufman Yotam , Eshar Shiri , Ron Dzikowski
Published: January 2021

Plasmodium falciparum, the parasite responsible for the deadliest form of human malaria, maintains a complex life cycle with a relatively small number of genes.PfSR1 is an alternative splicing factor that regulates expansion of theP. falciparumprotein repertoire. To further investigatePfSR1 functions, we set to unveil its interactome. We found thatPfSR1 interacts with proteins, which are linked to various processes of RNA metabolism in a stage-dependent manner. These include: chromatin re-modeling, transcription, splicing and translation. Intriguingly, some of thePfSR1 interacting proteins are orthologues of proteins implicated in the DNA damage response. We demonstrate thatPfSR1 expression is important for preventing the accumulation of DNA damage in proliferating parasites. In addition, following parasites’ exposure to a source of DNA damage,PfSR1 is recruited to damaged foci where it interacts with the phosphorylated core histonePfH2A, which marks damaged chromatin. Furthermore,PfSR1 expression was found to be essential for the ability of the parasite to activate the DNA repair machinery and recover from DNA damage caused by either irradiation or exposure to artemisinin, the first line anti-malarial drug. These findings unveil a novel role ofPfSR1 in protectingP. falciparumfrom DNA damage and artemisinin exposure.
Deficiency of gluconeogenic enzyme PCK1 promotes non-alcoholic steatohepatitis progression and fibrosis through PI3K/AKT/PDGF axis activation
Authors: Ye Qian , Liu Yi , Zhang Guiji , Deng Haijun , Wang Xiaojun , Tuo Lin , Chen Chang , Pan Xuanming , Wu Kang , Fan Jiangao , Pan Qin , Wang Kai , Huang Ailong , Tang Ni
Published: January 2021

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by hepatic lipid accumulation, inflammation, and progressive fibrosis. We demonstrated that phosphoenolpyruvate carboxykinase 1 (PCK1) plays a central role in NASH progression. Mice with liverPck1deficiency fed a normal diet displayed hepatic lipid disorder and liver injury, whereas fibrosis and inflammation were aggravated in mice fed a NASH diet. Forced expression of PCK1 by adeno-associated virus in the liver ameliorated NASH in mice. PCK1 deficiency stimulated lipogenic gene expression and lipid synthesis. Moreover, loss of hepatic PCK1 activated the RhoA/PI3K/AKT pathway by increasing intracellular GTP levels, increasing secretion of platelet-derived growth factor-AA (PDGF-AA), and promoting hepatic stellate cell activation. Treatment with RhoA and AKT inhibitors or gene silencing of RhoA or AKT1 alleviated NASH progressionin vivo. Hepatic PCK1 deficiency may be important in hepatic steatosis and fibrosis development through paracrine secretion of PDGF-AA, highlighting a therapeutic strategy for NASH.
Moderate increases in channel discharge are positively related to ecosystem respiration in forested Ozark streams
Authors: Dodd Allyn K. , Magoulick Daniel D. , Evans-White Michelle A.
Published: January 2021

The natural flow regime is considered the “master variable” in lotic systems, controlling structure and function at organismal, population, community, and ecosystem levels. We sought to estimate forested headwater stream metabolism across two dominant flow regimes (RunoffandGroundwater) in northern Arkansas and evaluate potential differences in, and drivers of, gross primary production, ecosystem respiration, and net ecosystem metabolism. Flow regimes differed in intermittency, substrate heterogeneity, hyporheic connectivity, and dominant water source (subsurface runoff vs. groundwater), which we expected to result in differences in primary production and respiration. Average daily gross primary production (GPP) and ecosystem respiration (ER) estimated from field data collected from May 2015-June 2016 tended to be greater inGroundwaterstreams. Respiration was positively related to discharge (R2= 0.98 p< 0.0001) and net metabolism became more heterotrophic with increasing average annual discharge across sites (R2= 0.94, p= 0.0008). Characterizing ecosystem-level responses to differences in flow can reveal mechanisms governing stream metabolism and, in turn, provide information regarding trophic state and energy inputs as efforts continue to determine global trends in aquatic carbon sources and fates.
Conserved and unique transcriptional features of pharyngeal arches in the skate (Leucoraja erinacea) and evolution of the jaw
Authors: Hirschberger Christine , Sleight Victoria A. , Criswell Katharine E. , Clark Stephen J. , Gillis J. Andrew
Published: January 2021

The origin of the jaw is a long-standing problem in vertebrate evolutionary biology. Classical hypotheses of serial homology propose that the upper and lower jaw evolved through modifications of dorsal and ventral gill arch skeletal elements, respectively. If the jaw and gill arches are derived members of a primitive branchial series, we predict that they would share common developmental patterning mechanisms. Using candidate and RNAseq/differential gene expression analyses, we find broad conservation of dorsoventral patterning mechanisms within the developing mandibular, hyoid and gill arches of a cartilaginous fish, the skate (Leucoraja erinacea). Shared features include expression of genes encoding members of the ventralising BMP and endothelin signalling pathways and their effectors, the joint markers bapx1 and gdf5 and pro-chondrogenic transcription factors barx1 and gsc, and the dorsalising transcription factor pou3f3. Additionally, we find that mesenchymal expression ofeya1/six1is an ancestral feature of the mandibular arch of jawed vertebrates, while differences in notch signalling distinguish the mandibular and gill arches in skate. Comparative transcriptomic analyses of mandibular and gill arch tissues reveal additional genes differentially expressed along the dorsoventral axis of the pharyngeal arches, includingscamp5as a novel marker of the dorsal mandibular arch, as well as distinct transcriptional features of mandibular and gill arch muscle progenitors and developing gill buds. Taken together, our findings reveal conserved patterning mechanisms in the pharyngeal arches of jawed vertebrates, consistent with serial homology of their skeletal derivatives, as well as unique transcriptional features that may underpin distinct jaw and gill arch morphologies.
Differential expression of striatal proteins in a mouse model of DOPA-responsive dystonia reveals shared mechanisms among dystonic disorders
Authors: Briscione Maria A. , Dinasarapu Ashok R. , Bagchi Pritha , Donsante Yuping , Downs Anthony M. , Fan Xueliang , Hoehner Jessica , Jinnah H.A. , Hess Ellen J.
Published: January 2021

Dystonia is characterized by involuntary muscle contractions that cause debilitating twisting movements and postures. Although basal ganglia dysfunction is implicated in many forms of dystonia, the underlying mechanisms are unclear. Therefore, to reveal abnormal striatal cellular processes and pathways implicated in dystonia, we used an unbiased proteomic approach in a knockin mouse model of DOPA-responsive dystonia, a model in which the striatum is known to play a central role in the expression of dystonia. Fifty-seven of the 1805 proteins identified were differentially regulated in DOPA-responsive dystonia mice compared to control mice. Most differentially regulated proteins were associated with gene ontology terms that implicated either mitochondrial or synaptic dysfunction whereby proteins associated with mitochondrial function were generally over-represented whereas proteins associated with synaptic function were largely under-represented. Remarkably, nearly 20% of the differentially regulated proteins identified in our screen are associated with pathogenic variants that cause inherited dystonic disorders in humans suggesting shared mechanisms across many different forms of dystonia.
The Necroptosis Effector MLKL drives Small Extracellular Vesicle Release and Tumour Growth in Glioblastoma
Authors: André-Grégoire Gwennan , Douanne Tiphaine , Thys An , Maghe Clément , Jacobs Kathryn , Ballu Cyndie , Trillet Kilian , Busnelli Ignacio , Hyenne Vincent , Goetz Jacky G , Bidère Nicolas , Gavard Julie
Published: January 2021

Extracellular vesicles (EVs) are lipid-based nano-sized particles that convey biological material from donor to recipient cells. They play key roles in tumour progression, notably in glioblastoma in which the subpopulation of Glioblastoma Stem-like Cells (GSCs) might represent a meaningful source of tumour-derived EVs. However, the mechanisms involved in the production and release of EVs by GSCs are still poorly understood. Here, we report the identification of MLKL, a crucial effector of cell death by necroptosis, as a regulator of the constitutive secretion of small EVs from GSCs. The targeting of MLKL by genetic, protein depletion or chemical approaches alters endosomal trafficking and EV release and reduces GSC expansionin vitro. This function ascribed to MLKL appears independent of its role during necroptosis.In vivo, pharmacological inhibition of MLKL triggers a reduction of both the tumour burden in xenografted mice and of the level of plasmatic EVs. This work reinforces the idea of a non-deadly role for MLKL in endosomal trafficking and suggests that interfering with EV biogenesis is a promising therapeutic option to sensitize glioblastoma cells to death.
CoSTA: Unsupervised Convolutional Neural Network Learning for Spatial Transcriptomics Analysis
Authors: Xu Yang , McCord Rachel Patton
Published: January 2021

The rise of spatial transcriptomics technologies is leading to new insights about how gene regulation happens in a spatial context. Here, we present CoSTA: a novel approach to learn spatial similarities between gene expression matrices via convolutional neural network (ConvNet) clustering. By analyzing simulated and previously published spatial transcriptomics data, we demonstrate that CoSTA learns spatial relationships between genes in a way that emphasizes whole patterns rather than pixel-level correlation. CoSTA provides a quantitative measure of how similar each pair of genes are by their spatial pattern rather than only classifying genes into categories. We find that CoSTA identifies narrower, but biologically relevant, sets of significantly related genes as compared to other approaches.
Economic and environmental effects of replacing bottom trawling with fishing with creels
Authors: Hammarlund Cecilia , Jonsson Patrik , Valentinsson Daniel , Waldo Staffan
Published: January 2021

Bottom trawling is associated with negative external effects such as seafloor pressure and high fuel use. Replacing bottom trawls with passive gear, such as creels, is therefore interesting for policymakers. We investigate the response of the Norway lobster fishery in Sweden to an expanded creel area. Using an economic model (FishRent), we analyse fleet structure, net present value and two environmental indicators under five management scenarios. Our results show that expanding the creel area increases the number of creel fishers, while some trawlers leave the fishery. In total, the net present value and the environmental performance of the fishery improve.
Guardians of Democracy? On the Response of Civil Society Organisations to Right‐Wing Extremism
Authors: Lundberg Erik
Published: January 2021

This article expands on the understanding of the role civil society organisations (CSOs) play in counteracting right‐wing extremism. Drawing on central strands in the defending democracy literature, this article introduces a typology to classify the responses of CSOs to right‐wing extremism. The typology takes into account the distinction between tolerance and intolerance on the one hand, and active and passive political participation on the other. What is more, it allows for a more fine‐tuned analysis of a variety of CSO responses vis‐à‐vis extreme right‐wing movements. This distinction is important as it allows for a better understanding of the democratic role of civil society in general and the responses of pro‐democratic civil society to political extremism in particular. Using this typology as a point of departure, the article contributes empirically by exploring how local CSOs in the Swedish town of Ludvika responded to the foremost neo‐Nazi movement in the Nordic countries, namely the Nordic Resistance Movement (NRM), prior to the 2018 Swedish election. Drawing primarily on the perspective of civil society leaders, the findings show that local CSOs are generally intolerant of the NRM and have engaged in opposition to the movement. Notably, responses tend to be more oriented towards promoting dialogue and the importance of public discussion in civil society rather than using confrontational tactics such as protests and civil disobedience. The article concludes that CSOs serve as bulwarks against right‐wing extremism at least during politically charged situations; however, differences in tolerance and political participation indicate that CSOs respond differently to right‐wing extremism.
Adjunctive treatments for the management of septic shock – a narrative review of the current evidence
Authors: Donovan K. , Shah A. , Day J. , McKechnie S. R.
Published: January 2021

Septic shock is a leading cause of death and morbidity worldwide. The cornerstones of management include prompt identification of sepsis, early initiation of antibiotic therapy, adequate fluid resuscitation and organ support. Over the past two decades, there have been considerable improvements in our understanding of the pathophysiology of sepsis and the host response, including regulation of inflammation, endothelial disruption and impaired immunity. This has offered opportunities for innovative adjunctive treatments such as vitamin C, corticosteroids and beta‐blockers. Some of these approaches have shown promising results in early phase trials in humans, while others, such as corticosteroids, have been tested in large, international, multicentre randomised controlled trials. Contemporary guidelines make a weak recommendation for the use of corticosteroids to reduce mortality in sepsis and septic shock. Vitamin C, despite showing initial promise in observational studies, has so far not been shown to be clinically effective in randomised trials. Beta‐blocker therapy may have beneficial cardiac and non‐cardiac effects in septic shock, but there is currently insufficient evidence to recommend their use for this condition. The results of ongoing randomised trials are awaited. Crucial to reducing heterogeneity in the trials of new sepsis treatments will be the concept of enrichment, which refers to the purposive selection of patients with clinical and biological characteristics that are likely to be responsive to the intervention being tested.
Implant soft tissue Dehiscence coverage Esthetic Score (IDES): A pilot within‐ and between‐rater analysis of consistency in objective and subjective scores
Authors: Zucchelli Giovanni , Barootchi Shayan , Tavelli Lorenzo , Stefanini Martina , Rasperini Giulio , Wang Hom‐Lay
Published: January 2021

Objectives

To introduce an esthetic index for assessing the outcomes of peri‐implant soft tissue dehiscence/deficiency (PSTD) coverage and test its within‐ and between‐reviewer reliability.

Materials and Methods

Photographs of 51 single PSTDs at baseline and after treatment were provided to four periodontists from three centers. The examiners were asked to rate each case at two timepoints with the Implant soft tissue Dehiscence/deficiency coverage Esthetic Score (IDES) that involved the evaluation of the post‐treatment level of the soft tissue margin, peri‐implant papillae height, mucosa color, and mucosa appearance (summing up to a total score of 10). Variance components analysis was conducted using multilevel regression fit in a Bayesian framework for obtaining uncertainty intervals for fractional variance contributions and intraclass correlation values (ICC) of the IDES, and for each of its four clinical variables.

Results

Regression models showed reproducible esthetic evaluation among the examiners (inter‐reliability) and negligible intra‐reviewer variability (assessment of the same case at different timepoints). The ICC for the variability in the assessment of the overall IDES was 0.86, and for the individual components ranged from 0.78 to 0.87. Additionally, there was a strong similarity between the raters’ IDES values, and their subjective esthetic response, by the same raters.

Conclusion

The IDES showed persistent judgment among the 4 reviewers, and only a slight intra‐reviewer variability across timepoints. Within its limitations, this study suggests that the proposed novel score can be a reliable tool for evaluating the esthetic outcomes of PSTD coverage, which can aid in standardization of esthetic assessments following the treatment of a PSTD.
Innovative method to diagnose coronary Cameral fistula by contrast echocardiography
Authors: Eldeib Moustafa , Qaddoura Fatema , Sadek Marwan , Abuelatta Reda , Nagib Ayman
Published: January 2021

Introduction

Coronary artery fistula (CAF) is a rare cardiac anomaly that typically presents as a continuous murmur in an otherwise asymptomatic patient. Occasionally, it can result in congestive heart failure or bacterial endocarditis.

Objective

To better delineate the course of coronary artery fistula using an intracoronary injection of SonoVue contrast agent, while performing transthoracic echocardiography.

Method and results

A referred 46‐year‐old man, with a history of exertional dyspnea for almost 3 months, was admitted to the hospital with progressive dyspnea and assessed under suspicion of CAF. CAF was seen with a coronary angiogram, but the exact entry point in the left ventricle or left atrial wall could not be determined. CT angiography also failed to establish the drainage site, so CAG (coronary angiography) was repeated with the SonoVue contrast agent injected into LM (Left main) while using a Siemens echocardiography machine. Multiple views were obtained during the injection and revealed unusual flow in the left ventricle just below the PML (posterior mitral leaflet) and passing through the fistula to LV.

Conclusion

Contrast‐enhanced echocardiography by direct intracoronary injection of SonoVue contrast agent is safe and can aid in the delineation of fistula drainage.
Efficacy study of the new polycaprolactone thread compared with other commercialized threads in a murine model
Authors: Cho Seung Woo , Shin Byung Ho , Heo Chan Yeong , Shim Jung Hee
Published: January 2021

Background

Polydioxanone (PDO) threads, poly‐L‐lactic acid (PLLA) threads, and polycaprolactone (PCL) threads have been used for lifting and antiaging purposes. The new PCL threads that have less residual monomer compared to the previous PCL are developed.

Aims

The efficacy of threads regarding collagen synthesis and wrinkle improvement was evaluated in vivo model.

Methods

In this study, threads were inserted into 30 six‐week‐old male SKH‐1 hairless mice. One of four threads was implanted at either side of the spine of each mouse. Biopsy specimens obtained at 1, 4, and 8 weeks were examined using hematoxylin and eosin (H&E) and Herovici's stain. Additionally, immunoblot analysis was performed using primary antibody for collagen type III and transforming growth factor‐β (TGF‐β) and visualized by chemiluminescence and densitometric quantification. Finally, skin replicas were used to calculate total wrinkle area (mm2).

Results

Neocollagenesis was significantly increased by 50% in the new PCL and pre‐existing PCL groups at 8 weeks (p value < 0.001). Additionally, new‐PCL‐implanted mice showed a significant increase in collagen type III and TGF‐β expressions at 8 weeks (p value < 0.001). The number of inflammatory cells was also increased in the skin of PCL‐implanted mice at 8 weeks. Finally, wrinkles were reduced about 20% in the new PCL group at 8 weeks.

Conclusions

The new PCL thread exhibited a superior skin rejuvenation effect. This suggests that the material processing technology can be applied not only to the thread but also to various products such as dermal filler and cosmetics.
The spread of infectious asexuality through haploid pollen
Authors: Mau Martin , Liiving Tiina , Fomenko Liza , Goertzen Richard , Paczesniak Dorota , Böttner Laura , Sharbel Timothy F.
Published: January 2021

The mechanisms of initiation and transmission of apomixis (asexual reproduction through seeds) in natural plant populations are important for understanding the evolution of reproductive variation. Here, we used the phylogenetic diversity of the genus Boechera (Brassicaceae), together with natural diversity in pollen types produced by apomictic lines, to test whether hybridization triggers the transition to asexuality, and whether a ‘triploid bridge’ is required for the formation of polyploid apomicts.

We performed crosses between diploid sexual recipient and diploid apomictic donor lines and tested whether the mating system (interspecific hybridization vs intraspecific outcrossing) or pollen type (haploid vs diploid) influenced the transmission of apomixis from diploid apomictic donors into sexual recipients. We used genetic markers and flow cytometric analyses of embryo and endosperm in seeds to infer the reproductive mode.

Within a single generation, initiation of both diploid and polyploid apomixis in sexual Boechera can occur. Diploid apomixis is transmitted through haploid pollen (infectious asexuality) and polyploids can form through multiple pathways. The three functional elements of apomixis occasionally segregate.

Variation in pollen ploidy and the segregation of apomixis elements drive reproductive diversity of hybrids and outcrosses and can be utilized for apomixis initiation in crop breeding programs.
Alteration of lipids and amino acids in plasma distinguish schizophrenia patients from controls: A targeted metabolomics study
Authors: Liu Yiyun , Song Xuemian , Liu Xinyu , Pu Juncai , Gui Siwen , Xu Shaohua , Tian Lu , Zhong Xiaogang , Zhao Libo , Wang Haiyang , Liu Lanxiang , Xu Guowang , Xie Peng
Published: January 2021

Background

Schizophrenia (SCZ) is a serious psychiatric disorder. Metabolite disturbance is an important pathogenic factor in schizophrenic patients. In this study, we aim to identify plasma lipid and amino acid biomarkers for SCZ using targeted metabolomics.

Methods

Plasma from 76 SCZ patients and 50 matched controls were analyzed using the LC/MS‐based multiple reaction monitoring (MRM) metabolomics approach. A total of 182 targeted metabolites, including 22 amino acids and 160 lipids or lipid‐related metabolites were observed. We used binary logistic regression analysis to determine whether the lipid and amino acid biomarkers could discriminate SCZ patients from controls. The area under the curve (AUC) from receiver operation characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance of the biomarkers panel.

Results

We identified 19 significantly differentially expressed metabolites between the SCZ patients and the controls (false discovery rate < 0.05), including one amino acid and 18 lipids or lipid‐related metabolites. The binary logistic regression‐selected panel showed good diagnostic performance in the drug‐naïve group (AUC = 0.936) and all SCZ patients (AUC = 0.948), especially in the drug‐treated group (AUC = 0.963).

Conclusions

Plasma lipids and amino acids showed significant dysregulation in SCZ, which could effectively discriminate SCZ patients from controls. The LC/MS/MS‐based approach provides reliable data for the objective diagnosis of SCZ.
Characterizing reduced height wheat mutants for traits affecting abiotic stress and photosynthesis during seedling growth
Authors: Mohan Amita , Grant Nathan P. , Schillinger William F. , Gill Kulvinder S.
Published: January 2021

Most high‐yielding, semidwarf wheat (Triticum aestivum L.) grown around the world contains either Rht1 or Rht2 genes. The success of these high‐yielding cultivars is greatest in the most productive farming environments but provide marginal benefits in less favorable growing conditions such as shallow soils and low‐precipitation dryland farming. Further, growing evidence suggests semidwarf genes not only affect early seedling growth but limit grain yield, especially under abiotic stress conditions. There are 23 other reduced‐height mutants reported in wheat, most of which have not been functionally characterized. We evaluated these mutants along with their parents for several traits affecting seedling emergence, early seedling growth, and photosynthetic efficiency. Two‐ to seven‐fold differences in coleoptile length, first leaf length, root length, and root angle were observed among the genotypes. Most of the mutations had a positive effect on root length, while the root angle narrowed. Coleoptile and first leaf lengths were strongly correlated with emergence. A specialized deep planting experiment identified Rht5, Rht6, Rht8, and Rht13 with significantly improved seedling emergence compared to the parent. Among the mutants, Rht4, Rht19, and Rht12 ranked highest for photosynthetic traits while Rht9, Rht16, and Rht15 performed best for early seedling growth parameters. Considering all traits collectively, Rht15 showed the most promise for utilization in marginal environments followed by Rht19 and Rht16. These wheat mutants may be useful for deciphering the underlying molecular mechanisms of understudied traits and breeding programs in arid and semiarid regions where deep planting is practiced.
Plant aquaporins alleviate drought tolerance in plants by modulating cellular biochemistry, root‐architecture, and photosynthesis
Authors: Patel Jaykumar , Mishra Avinash
Published: January 2021

Water is a vital resource for plants to grow, thrive, and complete their life cycle. In recent years, drastic changes in the climate, especially drought frequency and severity, have increased, which reduces agricultural productivity worldwide. Aquaporins are membrane channels belonging to the major intrinsic protein superfamily, which play an essential role in cellular water and osmotic homeostasis of plants under both control and water deficit conditions. A genome‐wide search reveals the vast availability of aquaporin isoforms, phylogenetic relationships, different families, conserved residues, chromosomal locations, and gene structure of aquaporins. Furthermore, aquaporins gating and subcellular trafficking are commonly controlled by phosphorylation, cytosolic pH, divalent cations, reactive oxygen species, and stoichiometry. Researchers have identified their involvement in regulating hydraulic conductance, root system architecture, modulation of abiotic stress‐related genes, seed viability and germination, phloem loading, xylem water exit, photosynthetic parameters, and post‐drought recovery. Remarkable effects following the change in aquaporin activity and/or gene expression have been observed on root water transport properties, nutrient acquisition, physiology, transpiration, stomatal aperture, gas exchange, and water use efficiency. The present review highlights the role of different aquaporin homologs under water‐deficit stress condition in model and crop plants. Moreover, the opportunity and challenges encountered to explore aquaporins for engineering drought‐tolerant crop plants are also discussed here.
Assessing support for Blaberoidea phylogeny suggests optimal locus quality
Authors: Evangelista Dominic , Simon Sabrina , Wilson Megan M. , Kawahara Akito Y. , Kohli Manpreet K. , Ware Jessica L. , Wipfler Benjamin , Béthoux Olivier , Grandcolas Philippe , Legendre Frédéric
Published: January 2021

Phylogenomics seeks to use next‐generation data to robustly infer an organism's evolutionary history. Yet, the practical caveats of phylogenomics motivate investigation of improved efficiency, particularly when quality of phylogenies are questionable. To achieve improvements, one goal is to maintain or enhance the quality of phylogenetic inference while severely reducing dataset size. We approach this by assessing which kinds of loci in phylogenomic alignments provide the majority of support for a phylogenetic inference of cockroaches in Blaberoidea. We examine locus substitution rate, saturation, evolutionary divergence, rate heterogeneity, stabilizing selection, and a priori information content as traits that may determine optimality. Our controlled experimental design is based on 265 loci for 102 blaberoidean taxa and 22 outgroup species. Loci with high substitution rate, low saturation, low sequence distance, low rate heterogeneity, and strong stabilizing selection derive more support for phylogenetic relationships. We found that some phylogenetic information content estimators may not be meaningful for assessing information content a priori. We use these findings to design concatenated datasets with an optimized subsample of 100 loci. The tree inferred from the optimized subsample alignment was largely identical to that inferred from all 265 loci but with less evidence of long branch attraction, improved statistical support, and potential 4‐6x improvements to computation time. Supported by phylogenetic and morphological evidence, we erect three newly named clades (Anallactinae Evangelista & Wipfler subfam. nov., Orkrasomeria tax. nov. Evangelista, Wipfler, & Béthoux and Hemithyrsocerini Evangelista tribe nov.) and propose other taxonomic modifications. The diagnosis of Pseudophyllodromiidae Grandcolas, 1996 is modified to accommodate Anallactinae and Pseudophyllodromiinae Vickery & Kevan, 1983. The diagnosis of Ectobiidae Brunner von Wattenwyl, 1865 is modified to add novel morphological characters.
Experimental Investigation of Innovative Cooling Schemes on an Additively Manufactured Engine Scale Turbine Nozzle Guide Vane
Authors: Hossain Mohammad A. , Ameri Ali , Gregory James W. , Bons Jeffrey P.
Published: January 2021

This study includes the design, validation, and fabrication via direct metal laser sintering (DMLS) of a gas turbine nozzle guide vanes (NGV) that incorporates three innovative cooling schemes specifically enabled by additive manufacturing. The novel NGV design is the culmination of an extensive research and development effort over a period of 4 years that included low- and high-speed cascade testing coupled with unsteady computational fluid dynamics for numerous candidate innovative cooling architectures. The final vane design (SJ-vane) consists of sweeping jet (SJ) film cooling holes on the suction surface (SS), sweeping jet impingement holes at the leading edge and double-wall partial length triangular pin-fin with impinging jet at the trailing edge. For comparison purposes, a second DMLS enabled vane (777-vane) was designed and fabricated with prototypical cooling circuits to serve as a baseline. This vane consists of a shaped film cooling holes on the suction surface, circular impingement holes at the leading edge, and full-length cylindrical pin-fins at the trailing edge. Experiments with the two DMLS enabled vanes were performed at the Ohio State University Turbine Reacting Flow Rig (TuRFR) at engine-relevant temperature (1375 K) and Mach number conditions. Infrared (IR) thermography was utilized to measure the wall temperature of the pressure and suction surface at several coolant mass flowrates to estimate the overall cooling effectiveness (ϕ). Results showed improved cooling performance for the advanced cooling schemes (sweeping jet film cooling, impingement cooling, and triangular pin-fin cooling) compared with the baseline cooling schemes.
Short-Term Prediction of Global Solar Radiation Energy Using Weather Data and Machine Learning Ensembles: A Comparative Study
Authors: Al-Hajj Rami , Assi Ali , Fouad Mohamad
Published: January 2021

The ability to predict solar radiation one-day-ahead is critical for the best management of renewable energy tied-grids. Several machine learning ensemble techniques have been proposed to enhance the short-term prediction of solar radiation strength. In general, finding an optimal ensemble model that consists of combining individual predictors is not trivial due to the need for tuning and other related issues. Few comparative studies have been presented to obtain optimal structures of machine learning ensemble that deal with predicting solar radiation. The contribution of the present research consists of a comparative study of various structures of stacking-based ensembles of data-driven machine learning predictors that are widely used nowadays to conclude the best stacking strategies in terms of performance to combine predictors of solar radiation. The base individual predictors are arranged to predict solar radiation intensity using historical weather and solar radiation records. Three stacking techniques, namely, feed-forward neural networks, support vector regressors, and k-nearest neighbor regressors, have been examined and compared to combine the prediction outputs of base learners. Most of the examined stacking models have been found capable to predict the solar radiation, but those related to combining heterogeneous models using neural meta-models have shown superior performance. Furthermore, we have compared the performance of combined models against recurrent models. The solar radiation predictions of the surveyed models have been evaluated and compared over an entire year. The performance enhancements provided by each alternative ensemble have been discussed.
Wave Analysis for In-Plane Vibration of Angular and Curved Frames
Authors: Syam B. K. , Sarkar Abhijit
Published: January 2021

In many structural applications like bridges, arches, etc., frames are used, and it is important to study their dynamic behavior. Finite element method (FEM) is usually used for computational simulation of vibration for such frame structures. However, FEM simulations for high frequency are computationally intensive and lack accuracy. This paper proposes a wave propagation-based approach for the vibration analysis of a frame having angular and curved joints. The reflection and transmission matrices for the joints are derived using the kinematic compatibility and equilibrium conditions. Reflection, transmission, and propagation matrices are assembled leading to matrix equation terms of the wave amplitudes. Modal analysis and harmonic analysis of frames having curved and angular joints are performed using the present formulation. The frequency response function for point harmonic forcing acting on such structures is also presented. The formulation and the results are non-dimensionalized for wider applicability. The results obtained using the present formulation are compared with those obtained through FEM simulation in a commercial package. It is found that the results obtained using the two methods are in excellent correlation. The computational efficiency of the present method over FEM simulation is also reported.
Wake and Performance Predictions of Two- and Three-Bladed Wind Turbines Based on the Actuator Line Model1
Authors: Henao Garcia Sebastian , Benavides-Morán Aldo , Lopez Mejia Omar D.
Published: January 2021

This paper challenges the standard wind turbine design numerically assessing the wake and aerodynamic performance of two- and three-bladed wind turbine models implementing downwind and upwind rotor configurations, respectively. The simulations are conducted using the actuator line model (ALM) coupled with a three-dimensional Navier Stokes solver implementing the k−ω shear stress transport turbulence model. The sensitivity of the ALM to multiple simulation parameters is analyzed in detail and numerical results are compared against experimental data. These analyses highlight the most suitable Gaussian radius at the rotor to be equal to twice the chord length at 95% of the blade for a tip-speed ratio (TSR) of ten, while the Gaussian radius at the tower and the number of actuator points have a low incidence on the flow field computations overall. The numerical axial velocity profiles show better agreement upstream than downstream the rotor, while the discrepancies are not consistent through all the assessed operating conditions, thus highlighting that the ALM parameters are also dependent on the wind turbine's operating conditions rather than being merely geometric parameters. Particularly, for the upwind three-bladed wind turbine model, the accuracy of the total thrust computations improves as the TSR increases, while the least accurate wake predictions are found for its design TSR. Finally, when comparing both turbine models, an accurate representation of the downwind configuration is observed as well as realistic power extraction estimates. Indeed, the results confirm that rotors with fewer blades are more suitable to operate at high TSRs.