bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical Automaticity and Intercellular Synchronization via Shared Extracellular Compartments
Authors: Poelzing St. , Keener J. P
Published: April 2020

Electrically excitable cells often spontaneously and synchronously depolarize in vitro and in vivo. It remains unknown how cells synchronize and autorhythmically activate above the intrinsic mean activation frequency of isolated cells without pacemaking mechanisms. Recent insights into ephaptic coupling (non-gap junction or synaptic coupling) suggest that cyclic ion accumulation and depletion in diffusion limited extracellular volumes densely expressing ion channels modifies action potentials. This report explores how potassium accumulation and depletion in a restricted extracellular domain promotes spontaneous oscillations in the Hodgkin Huxley action potential model, which does not spontaneously activate on its own without external stimulus. Simulations demonstrate cells sharing a diffusion limited extracellular compartment can become autorhythmic and synchronous despite intercellular electrical heterogeneity. Autorhythmic frequency can be determined by net potassium flux into the cleft and the cleft volume. Additionally, inexcitable cells can induce autorhythmic activity in an excitable cell via a shared cleft and sufficient potassium fluxes contributed by each cell. Importantly, the synchronization and autorhythmic activity conferred by shared cleft with reduced potassium efflux can occur in the absence of gap junctions. Lastly, not only can potassium oscillations in shared restricted clefts initiate, support, and suppress autorhythmic depolarizations, the same mechanism can homogenize repolarization. The work has implications for understanding how automaticity is coordinated among excitable cells and suggests a new role for non-excitable cells such as fibroblasts, macrophages, or astrocytes with sarcolemmal potassium handling proteins facing shared and restricted intercellular clefts.

SIGNIFICANCE

A mechanism of cyclic ion accumulation and depletion in diffusion limited extracellular compartments can suppress, initiate, and support autorhythmic activity. Additionally, autorhythmicity can emerge from electrophysiologically heterogeneous cell pairs sharing a diffusion limited extracellular compartment, even if the individual cells will not spontaneously depolarize on their own. Sustained and synchronous autorhythmic activity can occur in the absence of gap junction coupling. Lastly, the shared diffusion limited extracellular compartment can also reduce action potential duration gradients by synchronizing repolarization.
RNA partitioning into stress granules is based on the summation of multiple interactions
Authors: Matheny Tyler , Van Treeck Briana , Huynh Thao Ngoc , Parker Roy
Published: April 2020

Stress granules (SGs) are stress-induced RNA-protein assemblies formed from a complex transcriptome of untranslating ribonucleoproteins (RNPs). Although RNAs can be either enriched or depleted from SGs, the rules that dictate RNA partitioning into SGs are unknown. We demonstrate that the SG-enrichedNORADRNA is sufficient to enrich a reporter RNA within SGs through the combined effects of multiple elements. Moreover, artificial tethering of G3BP1 or TIA1 can target mRNAs into SGs in a dose-dependent manner that suggests individual protein interactions have small effects on the SG partitioning of mRNPs, which is supported by the observation that the SG transcriptome is largely unchanged in cell lines lacking the abundant SG RNA-binding proteins G3BP1 and G3BP2. We suggest the targeting of RNPs into SGs is due to a summation of potential RNA-protein, protein-protein, and RNA-RNA interactions with no single interaction dominating RNP recruitment into SGs.
Predicting the Viability of Beta-Lactamase: How Folding and Binding Free Energies Correlate with Beta-Lactamase Fitness
Authors: Yang Jordan , Naik Nandita , Patel Jagdish Suresh , Wylie Christopher S. , Gu Wenze , Huang Jessie , Ytreberg Marty , Naik Mandar T. , Weinreich Daniel M. , Rubenstein Brenda M.
Published: April 2020

One of the long-standing holy grails of molecular evolution has been the ability to predict an organism’s fitness directly from its genotype. With such predictive abilities in hand, researchers would be able to more accurately forecast how organisms will evolve and how proteins with novel functions could be engineered, leading to revolutionary advances in medicine and biotechnology. In this work, we assemble the largest reported set of experimental TEM-1β-lactamase folding free energies and use this data in conjunction with previously acquired fitness data and computational free energy predictions to determine how much of the fitness ofβ-lactamase can be directly predicted by thermodynamic folding and binding free energies. We focus uponβ-lactamase because of its long history as a model enzyme and its central role in antibiotic resistance. Based upon a set of 21β-lactamase single and double mutants expressly designed to influence protein folding, we first demonstrate that modeling software such as FoldX and PyRosetta designed to compute folding free energies can meaningfully, although not perfectly, predict the experimental folding free energies of single mutants. Interestingly, while these techniques also yield sensible double mutant free energies, we show that they do so for the wrong physical reasons. We then go on to assess how well both experimental and computational folding free energies explain single mutant fitness. We find that folding free energies account for, at most, 24% of the variance inβ-lactamase fitness values according to linear models and, somewhat surprisingly, complementing folding free energies with computationally-predicted binding free energies of residues near the active site only increases the folding-only figure by a few percent. This strongly suggests that the majority ofβ-lactamase’s fitness is controlled by factors other than free energies. Overall, our results shed a bright light on to what extent the community is justified in using thermodynamic measures to infer protein fitness as well as how applicable modern computational techniques for predicting free energies will be to the large data sets of multiply-mutated proteins forthcoming.
TimeTrial: An Interactive Application for Optimizing the Design and Analysis of Transcriptomic Times-Series Data in Circadian Biology Research
Authors: Ness-Cohn Elan , Iwanaszko Marta , Kath William , Allada Ravi , Braun Rosemary
Published: April 2020

The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues, coordinating physiological processes. The effect of this rhythm on health has generated increasing interest in discovering genes under circadian control by searching for periodic patterns in transcriptomic time-series experiments. While algorithms for detecting cycling transcripts have advanced, there remains little guidance quantifying the effect of experimental design and analysis choices on cycling detection accuracy. We present TimeTrial, a user-friendly benchmarking framework using both real and synthetic data to investigate cycle detection algorithms’ performance and improve circadian experimental design. Results show that the optimal choice of analysis method depends on the sampling scheme, noise level, and shape of the waveform of interest; and provides guidance on the impact of sampling frequency and duration on cycling detection accuracy. The TimeTrial software is freely available for download and may also be accessed through a web interface. By supplying a tool to vary and optimize experimental design considerations, TimeTrial will enhance circadian transcriptomics studies.
Determining the probability of hemiplasy in the presence of incomplete lineage sorting and introgression
Authors: Hibbins Mark S. , Gibson Matthew J.S. , Hahn Matthew W.
Published: April 2020

Abstract

The incongruence of character states with phylogenetic relationships is often interpreted as evidence of convergent evolution. However, trait evolution along discordant gene trees can also generate these incongruences – a phenomenon known as hemiplasy. Classic phylogenetic comparative methods do not account for discordance, resulting in incorrect inferences about the number of times a trait has evolved, and therefore about convergence. Biological sources of discordance include incomplete lineage sorting (ILS) and introgression, but only ILS has received theoretical consideration in the context of hemiplasy. Here, we derive expectations for the probabilities of hemiplasy and homoplasy with ILS and introgression acting simultaneously. We find that introgression makes hemiplasy more likely than ILS alone, suggesting that methods that account for discordance only due to ILS will be conservative. We also present a method for making statistical inferences about the relative probabilities of hemiplasy and homoplasy in empirical datasets. Our method is implemented in the software packageHeIST(Hemiplasy Inference Simulation Tool), and estimates the most probable number of transitions among character states given a set of relationships with discordance.HeISTcan accommodate ILS and introgression simultaneously, and can be applied to phylogenies where the number of taxa makes finding an analytical solution impractical. We apply this tool to two empirical cases of apparent trait convergence in the presence of high levels of discordance, one of which involves introgression between the convergent lineages. In both cases we find that hemiplasy is likely to contribute to the observed trait incongruences.
In-field bioreactors demonstrate dynamic shifts in microbial communities in response to geochemical perturbations
Authors: Wilpiszeski Regina L. , Gionfriddo Caitlin M. , Wymore Ann M. , Moon Ji-Won , Lowe Kenneth A. , Podar Mircea , Rafie Sa’ad , Fields Matthew W. , Hazen Terry C. , Ge Xiaoxuan , Poole Farris , Adams Michael W.W. , Chakraborty Romy , Fan Yupeng , Nostrand Joy D. Van , Zhou Jizhong , Arkin Adam P. , Elias Dwayne A.
Published: April 2020

Subsurface microbial communities mediate the transformation and fate of redox sensitive materials including organic matter, metals and radionuclides. Few studies have explored how changing geochemical conditions influence the composition of groundwater microbial communities over time. We temporally monitored alterations in abiotic forces on microbial community structure using 1L in-field bioreactors receiving background and contaminated groundwater at the Oak Ridge Reservation, TN. Planktonic and biofilm microbial communities were initialized with background water for 4 days to establish communities in triplicate control reactors and triplicate test reactors and then fed filtered water for 14 days. On day 18, three reactors were switched to receive filtered groundwater from a contaminated well, enriched in total dissolved solids relative to the background site, particularly chloride, nitrate, uranium, and sulfate. Biological and geochemical data were collected throughout the experiment, including planktonic and biofilm DNA for 16S rRNA amplicon sequencing, cell counts, total protein, anions, cations, trace metals, organic acids, bicarbonate, pH, Eh, DO, and conductivity. We observed significant shifts in both planktonic and biofilm microbial communities receiving contaminated water. This included a loss of rare taxa, especially amongst members of theBacteroidetes,Acidobacteria,Chloroflexi, andBetaproteobacteria, but enrichment in the Fe- and nitrate-reducingFerribacteriumand parasiticBdellovibrio. These shifted communities were more similar to the contaminated well community, suggesting that geochemical forces substantially influence microbial community diversity and structure. These influences can only be captured through such comprehensive temporal studies, which also enable more robust and accurate predictive models to be developed.
Role of gene length in control of human gene expression: chromosome-specific and tissue-specific effects
Authors: Brown Jay C.
Published: April 2020

Background

This study was carried out to pursue the observation that the level of gene expression is affected by gene length in the genomes of higher vertebrates. As transcription is a time-dependent process, it is expected that gene expression will be inversely related to gene length, and this is found to be the case. Here I describe the results of studies performed with the human genome to test whether the gene length/gene expression linkage is affected by two factors, the chromosome where the gene is located and the tissue where it is expressed.

Experimental design

Studies were carried out with a database of 2413 human genes that were divided into short, mid-length and long groups. Each of the 24 human chromosomes was then characterized according to the proportion of each gene length group present. A similar analysis was performed with 19 human tissues. The proportion of short, mid-length and long genes was noted for each tissue.

Results

Both chromosome and tissue studies revealed new information about the role of gene length in control of gene expression. Chromosome studies led to the identification of two chromosome populations that differ in the level of short gene expression. Tissue studies support the conclusion that short, highly expressed genes are enriched in tissues that produce protein products that are exported from the host cell.
Structure of the bacterial cellulose ribbon and its assembly-guiding cytoskeleton by electron cryotomography
Authors: Nicolas William J. , Ghosal Debnath , Tocheva Elitza I. , Meyerowitz Elliot M. , Jensen Grant J.
Published: April 2020

Cellulose is a widespread component of bacterial biofilms, where its properties of exceptional water retention, high tensile strength and stiffness prevents dehydration and mechanical disruption of the biofilm. Bacteria in theGluconacetobactergenus secrete crystalline cellulose, with a structure very similar to that found in plant cell walls. How this higher-order structure is produced is poorly understood. We used cryo-electron tomography and focused ion beam milling of native bacterial biofilms to image cellulose-synthesizingG. hanseniiandG. xylinusbacteria in a frozen-hydrated, near-native state. We confirm previous results suggesting that cellulose crystallization occurs serially following its secretion along one side of the cell, leading to a cellulose ribbon that can reach several microns in length and combine with ribbons from other cells to form a robust biofilm matrix. We were able to take direct measurements in a near-native state of the cellulose sheets. Our results also reveal a novel cytoskeletal structure, that we name the cortical belt, adjacent to the inner membrane and underlying the sites where cellulose is seen emerging from the cell. We find that this structure is not present in other cellulose-synthesizing bacterial species,Agrobacterium tumefaciensandEscherichia coli1094, which do not produce organized cellulose ribbons. We therefore propose that the cortical belt holds the cellulose synthase complexes in a line, to form higher-order cellulose structures such as sheets and ribbons.
Delayed clearance of SARS-CoV2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs
Authors: Shastri Aditi , Wheat Justin , Agrawal Sachee , Chaterjee Nirjhar , Pradhan Kith , Goldfinger Mendel , Kornblum Noah , Steidl Ulrich , Verma Amit , Shastri Jayanthi
Published: April 2020

The novel coronavirus SARS-CoV2 has been observed to cause a higher incidence and greater severity of disease in males, as seen in multiple cohorts across the globe. The reasons for gender disparity in disease severity is unclear and can be due to host factors. To determine whether males have delayed viral clearance after infection, we evaluated the time to clearance in symptomatic patients tested by serial oropharyngeal/nasopharyngeal swabs followed by RT-PCR at a reference lab in Mumbai, India. A total of 68 subjects with median age of 37 years (3-75 range) were examined and included 48 (71%) males and 20 (29%) females. We observed that females were able to achieve viral clearance significantly earlier than males, with a median difference of 2 days in achieving a negative PCR result (P value = 0.038). Furthermore, examination of 3 families with both male and female patients followed serially, demonstrated that female members of the same household cleared the SARS-CoV2 infection earlier in each family. To determine reasons for delayed clearance in males, we examined the expression patterns of the SARS-CoV2 receptor, Angiotensin-converting enzyme 2 (ACE2), in tissue specific repositories. We observed that the testes was one of the highest sites of ACE2 expression in 3 independent RNA expression databases (Human Protein Atlas, FAMTOM5 and GETx). ACE2 was also determined to be highly expressed in testicular cells at the protein levels. Interestingly, very little expression of ACE2 was seen in ovarian tissue. Taken together, these observations demonstrate for the first time that male subjects have delayed viral clearance of SARS-CoV2. High expression of ACE2 in testes raises the possibility that testicular viral reservoirs may play a role in viral persistence in males and should be further investigated.
Outcomes of the 2019 Novel Coronavirus in patients with or without a history of cancer - a multi-centre North London experience
Authors: Joharatnam-Hogan Nalinie , Hochhauser Daniel , Shiu Kai-Keen , Rush Hannah , Crolley Valerie , Butcher Emma , Sharma Anand , Muhammad Aun , Anwar Muhammad , Vasdev Nikhil , Kantser Ganna , Saha Aramita , Raja Fharat , Bridgewater John , Khan Khurum
Published: April 2020

Background

Four months after the first known case of the 2019 novel coronavirus disease (COVID-19), on the 11th March 2020, the WHO declared the outbreak a pandemic and acknowledged the potential to overwhelm national healthcare systems. The high prevalence and associated healthcare, social and economic challenges of COVID-19 suggest this pandemic is likely to have a major impact on cancer management, and has been shown to potentially have worse outcomes in this cohort of vulnerable patients (1). This study aims to compare the outcomes of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed COVID-19 positive disease in patients with or without a history of cancer.

Method

We retrospectively collected clinical, pathological and radiological characteristics and outcomes of COVID-19 RT-PCR positive cancer patients treated consecutively in four different North London hospitals (cohort A). Outcomes recorded included morbidity, mortality and length of hospital stay. All clinically relevant outcomes were then compared to consecutively admitted COVID-19 positive patients, without a history of cancer (cohort B), treated at the primary centre during the same time period (12th March-7th April 2020).

Results

A total of 52 electronic patient records during the study time period were reviewed. Cohort A (median age 76 years, 56% males) and cohort B (median age 58 years, 62% male) comprised of 26 patients each. With the exclusion of cancer, both had a median of 2 comorbidities. Within cohort A, the most frequent underlying cancer was colorectal (5/26) and prostate cancer (5/26), and 77% of patients in Cohort A had received previous anti-cancer therapy. The most common presenting symptoms were cough and pyrexia in both cohorts. Frequent laboratory findings included lymphopenia, anaemia and elevated CRP in both cohorts, whilst hypokalaemia, hypoalbuminaemia and hypoproteinaemia was predominantly seen amongst patients with cancer. Median duration of admission was 7 days in both cohorts. The mortality rate was the same in both cohorts (23%), with median age of mortality of 80 years. Of cancer patients who died, all were advanced stage, had been treated with palliative intent and had received anti-cancer therapy within 13 days of admission.

Conclusion

Old age, late stage of cancer diagnosis and multiple co-morbidities adversely influence the outcome of patients with COVID-19 positive patients. Whilst extra caution is warranted in the administration of anti-cancer therapies pertaining to the risk of immune-suppression, this data does not demonstrate a higher risk to cancer patients compared to their non-cancer counterparts.
Changes in Sound Localization Performance of Single-Sided Deaf Listeners after Visual Feedback Training in Azimuth
Authors: Zonooz Bahram , Opstal A. John Van
Published: April 2020

Chronic single-sided deaf (CSSD) listeners lack the availability of binaural difference cues to localize sounds in the horizontal plane. Hence, for directional hearing they have to rely on different types of monaural cues: loudness perceived in their hearing ear, which is affected in a systematic way by the acoustic head shadow, on spectral cues provided by the low-pass filtering characteristic of the head, and on high-frequency spectral-shape cues from the pinna of their hearing ear. Presumably, these cues are differentially weighted against prior assumptions on the properties of sound sources in the environment. The rules guiding this weighting process are not well understood. In this preliminary study, we trained three CSSD listeners to localize a fixed intensity, high-pass filtered sound source at ten locations in the horizontal plane with visual feedback. After training, we compared their localization performance to sounds with different intensities, presented in the two-dimensional frontal hemifield to their pre-training results. We show that the training had rapidly readjusted the contributions of monaural cues and internal priors, which resulted to be imposed by the multisensory information provided during the training. We compare the results with the strategies found for the acute monaural hearing condition of normal-hearing listeners, described in an earlier study [1].
Phylogenomic terraces: presence and implication in species tree estimation from gene trees
Authors: Farah Ishrat Tanzila , Islam Md Muktadirul , Zinat Kazi Tasnim , Rahman Atif Hasan , Bayzid Md Shamsuzzoha
Published: April 2020

Species tree estimation from multi-locus dataset is extremely challenging, especially in the presence of gene tree heterogeneity across the genome due to incomplete lineage sorting (ILS).Summary methodshave been developed which estimate gene trees and then combine the gene trees to estimate a species tree by optimizing various optimization scores. In this study, we have formalized the concept of “phylogenomic terraces” in the species tree space, where multiple species trees with distinct topologies may have exactly the same optimization score (quartet score, extra lineage score, etc.) with respect to a collection of gene trees. We investigated the presence and implication of terraces in species tree estimation from multi-locus data by taking ILS into account. We analyzed two of the most popular ILS-aware optimization criteria:maximize quartet consistency(MQC) andminimize deep coalescence(MDC). Methods based on MQC are provably statistically consistent, whereas MDC is not a consistent criterion for species tree estimation. Our experiments, on a collection of dataset simulated under ILS, indicate that MDC-based methods may achieve competitive or identical quartet consistency score as MQC but could be significantly worse than MQC in terms of tree accuracy – demonstrating the presence and affect of phylogenomic terraces. This is the first known study that formalizes the concept of phylogenomic terraces in the context of species tree estimation from multi-locus data, and reports the presence and implications of terraces in species tree estimation under ILS.
Analytical models forβ-diversity and the power-law scaling ofβ-deviation
Authors: Xing Dingliang , He Fangliang
Published: April 2020

β-diversity is a primary biodiversity pattern for inferring community assembly. A randomized null model that generates a standardizedβ-deviation has been widely used for this purpose. However, the null model has been much debated and its application is limited to abundance data.

Here we derive analytical models forβ-diversity to address the debate, clarify the interpretation, and extend the application to occurrence data.

The analytical analyses show unambiguously that the standardizedβ-deviation is a quantification of the effect size of non-random spatial distribution of species onβ-diversity for a given species abundance distribution. It robustly scales with sampling effort following a power law with exponent of 0.5. This scaling relationship offers a simple method for comparingβ-diversity of communities of different sizes.

Assuming logseries distribution for the metacommunity species abundance distribution, our model allows for calculation of the standardizedβ-deviation using occurrence data plus a datum on the total abundance.

Our theoretical model justifies and generalizes the use of theβnull model for inferring community assembly rules.
Lysosomal activity regulatesCaenorhabditis elegansmitochondrial dynamics through vitamin B12 metabolism
Authors: Wei Wei , Ruvkun Gary
Published: April 2020

Mitochondrial fission and fusion are highly regulated by energy demand and physiological conditions to control the production, activity, and movement of these organelles. Mitochondria are arrayed in a periodic pattern inCaenorhabditis elegansmuscle, but this pattern is disrupted by mutations in the mitochondrial fission component dynamin. Here we show that the dramatically disorganized mitochondria caused by a mitochondrial fission-defective dynamin mutation is strongly suppressed to a more periodic pattern by a second mutation in lysosomal biogenesis or acidification. Vitamin B12 is normally imported from the bacterial diet via lysosomal degradation of B12-binding proteins and transport of vitamin B12 to the mitochondrion and cytoplasm. We show that the lysosomal dysfunction induced by gene inactivations of lysosomal biogenesis or acidification factors causes vitamin B12 deficiency. Growth of theC. elegansdynamin mutant on anE. colistrain with low vitamin B12 also strongly suppressed the mitochondrial fission defect. Of the twoC. elegansenzymes that require B12, gene inactivation of methionine synthase suppressed the mitochondrial fission defect of a dynamin mutation. We show that lysosomal dysfunction induced mitochondrial biogenesis which is mediated by vitamin B12 deficiency and methionine restriction. S-adenosylmethionine, the methyl donor of many methylation reactions, including histones, is synthesized from methionine by S-adenosylmethionine synthase; inactivation of thesams-1S-adenosylmethionine synthase also suppresses thedrp-1fission defect, suggesting that vitamin B12 regulates mitochondrial biogenesis and then affects mitochondrial fission via chromatin pathways.

SIGNIFICANCE STATEMENT

The balance of mitochondrial fission and fusion, two aspects of mitochondrial dynamics, is important for mitochondrial function. Here we show thatCaenorhabditis eleganslysosomal activity regulates mitochondrial dynamics by affecting mitochondrial fission through interfering the metabolism of a micronutrient, vitamin B12. Vitamin B12 is exclusively obtained from diets in animals includingC. elegansand humans, and its uptake is mediated by the lysosome. We show that lysosomal dysfunction causes vitamin B12 deficiency that leads to reduction of methionine and S-adenosylmethionine to in turn increase mitochondrial biogenesis and fission. Our study provides an insight on the interactions between mitochondrial function and micronutrient metabolism.
Navigating the translational roadblock: Towards highly specific and effective all-optical interrogations of neural circuits
Authors: Fu Ting , Arnoux Isabelle , Döring Jan , Watari Hirofumi , Stasevicius Ignas , Stroh Albrecht
Published: April 2020

Two-photon (2-P) all-optical approaches combinein vivo2-P calcium imaging and 2-P optogenetic modulations and have the potential to build a framework for network-based therapies, e.g. for rebalancing maladaptive activity patterns in preclinical models of neurological disorders. Here, our goal was to tailor these approaches for this purpose: Firstly, we combinedin vivojuxtacellular recordings and GCaMP6f-based 2-P calcium imaging in layer II/III of mouse visual cortex to tune our detection algorithm towards a 100 % specific identification of AP-related calcium transients. False-positive-free detection was achieved at a sensitivity of approximately 73 %. To further increase specificity, secondly, we minimized photostimulation artifacts as a potential source for false-positives by using extended-wavelength-spectrum laser sources for optogenetic stimulation of the excitatory opsin C1V1. We achieved artifact-free all-optical experiments performing photostimulations at 1100 nm or higher and simultaneous calcium imaging at 920 nm in mouse visual cortexin vivo. Thirdly, we determined the spectral range for maximizing efficacy of optogenetic control by performing 2-P photostimulations of individual neurons with wavelengths up to 1300 nm. The rate of evoked transients in GCaMP6f/C1V1-co-expressing cortical neurons peaked already at 1100 nm. By refining spike detection and defining 1100 nm as the optimal wavelength for artifact-free and effective stimulations of C1V1 in GCaMP-based all-optical interrogations, we increased the translational value of these approaches, e.g. for the use in preclinical applications of network-based therapies.

One Sentence Summary

We maximize translational relevance of 2-P all-optical physiology by increasing specificity, minimizing artifacts and optimizing stimulation efficacy.
Generation of cardiac valve endocardial like cells from human pluripotent stem cells
Authors: Cheng LX , Song Y , Zhang YY , Geng YC , Xu WL , Wang Z , Wang L , Huang K , Dong NG , Sun YH
Published: April 2020

The cardiac valvular endothelial cells (VECs) are an ideal cell source that could be used for the fabrication of the next generation tissue-engineered cardiac valves (TEVs). However, few studies have been focused on the derivation of this important cell type. Here we describe a chemically defined xeno-free method for generating VEC-like cells from human pluripotent stem cells (hPSCs) through an intermediate endocardium stage. HPSCs were initially specified to KDR+/ISL1+multipotent cardiac progenitor cells (CPCs), followed by differentiation into endocardial progenitors under the combined treatment with VEGFA, BMP4 and bFGF. In the presence of VEGFA, BMP4 and TGFb, valve endocardial progenitor cells (VEPs) were efficiently derived from endocardial progenitors without a sorting step. Mechanistically, administration of TGFb and BMP4 may specify the VEP fate by facilitating the expression of key transcription factors ETV2 and NFATc1 at the immediate early stage and by activating Notch signaling at the later stage. Notch activation is likely an important part of VEP induction. HPSC-derived VEPs exhibited morphological, molecular and functional similarities to that of the primary VECs isolated from normal human aortic valves. When hPSC-derived VEPs were seeded onto the surface of the de-cellularized porcine aortic valve (DCV) matrix scaffolds, they exhibited higher proliferation and survival potential than the primary VECs. Our results suggest that hPSC-derived VEPs could serve as as a potential platform for the study of valve development, and as starting materials for the construction of the next generation TEVs.

Highlights

Valve endocardial progenitor cells (VEPs) could be efficiently derived from hPSCs without a sorting step

The combined treatment with TGFb and BMP4 induce VEP fate by enhancing the expression ofETV2andNFATc1

HPSC-derived VEPs resemble the isolated primary VECs molecularly, morphologically and functionally

HPSC-derived VEPs exhibit proliferative and functional potential similar to the primary VECs when seeded onto the DCVs
New zeolite-like RUB-5 and its related hydrous layer silicate RUB-6 structurally characterized by electron microscopy
Authors: Krysiak Yaşar , Marler Bernd , Barton Bastian , Plana-Ruiz Sergi , Gies Hermann , Neder Reinhard B. , Kolb Ute
Published: April 2020

This study made use of a recently developed combination of advanced methods to reveal the atomic structure of a disordered nanocrystalline zeolite using exit wave reconstruction, automated diffraction tomography, disorder modelling and diffraction pattern simulation. By applying these methods, it was possible to determine the so far unknown structures of the hydrous layer silicate RUB-6 and the related zeolite-like material RUB-5. The structures of RUB-5 and RUB-6 contain the same dense layer-like building units (LLBUs). In the case of RUB-5, these building units are interconnected via additional SiO4/2 tetrahedra, giving rise to a framework structure with a 2D pore system consisting of intersecting 8-ring channels. In contrast, RUB-6 contains these LLBUs as separate silicate layers terminated by silanol/siloxy groups. Both RUB-6 and RUB-5 show stacking disorder with intergrowths of different polymorphs. The unique structure of RUB-6, together with the possibility for an interlayer expansion reaction to form RUB-5, make it a promising candidate for interlayer expansion with various metal sources to include catalytically active reaction centres.
Conversion of 3-amino-4-arylamino-1H-isochromen-1-ones to 1-arylisochromeno[3,4-d][1,2,3]triazol-5(1H)-ones: synthesis, spectroscopic characterization and the structures of four products and one ring-opened derivative
Authors: Vicentes Daniel E. , Romero Andrea L. , Rodríguez Ricuarte , Cobo Justo , Glidewell Christopher
Published: April 2020

An efficient synthesis of 1-arylisochromeno[3,4-d][1,2,3]triazol-5(1H)-ones, involving the diazotization of 3-amino-4-arylamino-1H-isochromen-1-ones in weakly acidic solution, has been developed and the spectroscopic characterization and crystal structures of four examples are reported. The molecules of 1-phenylisochromeno[3,4-d][1,2,3]triazol-5(1H)-one, C15H9N3O2, (I), are linked into sheets by a combination of C—H...N and C—H...O hydrogen bonds, while the structures of 1-(2-methylphenyl)isochromeno[3,4-d][1,2,3]triazol-5(1H)-one, C16H11N3O2, (II), and 1-(3-chlorophenyl)isochromeno[3,4-d][1,2,3]triazol-5(1H)-one, C15H8ClN3O2, (III), each contain just one hydrogen bond which links the molecules into simple chains, which are further linked into sheets by π-stacking interactions in (II) but not in (III). In the structure of 1-(4-chlorophenyl)isochromeno[3,4-d][1,2,3]triazol-5(1H)-one, (IV), isomeric with (III), a combination of C—H...O and C—H...π(arene) hydrogen bonds links the molecules into sheets. When compound (II) was exposed to a strong acid in methanol, quantitative conversion occurred to give the ring-opened transesterification product methyl 2-[4-hydroxy-1-(2-methylphenyl)-1H-1,2,3-triazol-5-yl]benzoate, C17H15N3O3, (V), where the molecules are linked by paired O—H...O hydrogen bonds to form centrosymmetric dimers.
Ditopic halogen bonding with bipyrimidines and activated pyrimidines
Authors: Nwachukwu Chideraa I. , Patton Leanna J. , Bowling Nathan P. , Bosch Eric
Published: April 2020

The potential of pyrimidines to serve as ditopic halogen-bond acceptors is explored. The halogen-bonded cocrystals formed from solutions of either 5,5′-bipyrimidine (C8H6N4) or 1,2-bis(pyrimidin-5-yl)ethyne (C10H6N4) and 2 molar equivalents of 1,3-diiodotetrafluorobenzene (C6F4I2) have a 1:1 composition. Each pyrimidine moiety acts as a single halogen-bond acceptor and the bipyrimidines act as ditopic halogen-bond acceptors. In contrast, the activated pyrimidines 2- and 5-{[4-(dimethylamino)phenyl]ethynyl}pyrimidine (C14H13N3) are ditopic halogen-bond acceptors, and 1:1 halogen-bonded cocrystals are formed from 1:1 mixtures of each of the activated pyrimidines and either 1,2- or 1,3-diiodotetrafluorobenzene. A 1:1 cocrystal was also formed between 2-{[4-(dimethylamino)phenyl]ethynyl}pyrimidine and 1,4-diiodotetrafluorobenzene, while a 2:1 cocrystal was formed between 5-{[4-(dimethylamino)phenyl]ethynyl}pyrimidine and 1,4-diiodotetrafluorobenzene.
Aspect context aware sentiment classification of online consumer reviews
Authors: Bansal Barkha , Srivastava Sangeet
Published: April 2020

Purpose

Aspect based sentiment classification is valuable for providing deeper insight into online consumer reviews (OCR). However, the majority of the previous studies explicitly determine the orientation of aspect related sentiment bearing word and overlook the aspect-context. Therefore, this paper aims to propose an aspect-context aware sentiment classification of OCR for deeper and more accurate insights.

Design/methodology/approach

In the proposed methodology, first, aspect descriptions and sentiment bearing words are extracted. Then, the skip-gram model is used to extract the first set of features to capture contextual information. For the second category of features, cosine similarity is used between a pre-defined seed word list and aspects, to capture aspect context sensitive sentiments. The third set of features includes weighted word vectors using term frequency-inverse document frequency. After concatenating features, ensemble classifier is used using three base classifiers.

Findings

Experimental results on two real-world data sets with variable lengths, acquired from Amazon.com and TripAdvisor.com, show that the advised ensemble approach significantly outperforms sentiment classification accuracy of state-of-the-art and baseline methods.

Originality/value

This method is capable of capturing the correct sentiment of ambiguous words and other special words by extracting aspect-context using word vector similarity instead of expensive lexical resources, and hence, shows superior performance in terms of accuracy as compared to other methods.
Two-stage incentives system for commercial banks based on centralized resource allocation model in DEA-R
Authors: Kamyab Parisa , Mozaffari Mohammad Reza , Gerami Javad , Wankei Peter F.
Published: April 2020

Purpose

It is always of great importance for managers in organizations to evaluate their staff members and create incentive systems, using instruments such as Data Envelopment Analysis (DEA) and DEA-R (DEA models based on ratio analysis). The purpose of this paper is to propose a two-stage network incentives system for commercial banks.

Design/methodology/approach

Centralized Resource Allocation (CRA) models make it possible to project all decision-making units (DMUs) onto the efficient frontier by solving a single linear programming model. In this paper, we use our proposed DEA-R-based CRA models to evaluate commercial banks in a two-stage case when the only ratios available are the assets-to-costs and income-to-assets vectors.

Findings

Thirteen commercial banks modeled as two-stage networks were evaluated by the models proposed in two different cases of ratio data. Results suggest that the proposed methodology yields more accurate efficiency scores, thus allowing better discrimination among DMUs. Furthermore, evaluating the DMUs when they are structured as two-stage (or even three-stage) networks makes it possible to examine the incentives system in more detail. Therefore, the use of incentive systems by managers would allow a better focus on the priority activities of commercial banks and a faster movement toward the frontier of best practices.

Originality/value

The super-efficiency scores of a number of commercial banks are evaluated based on the CRA model, as a cornerstone criterion for the two-stage evaluation in DEA-R, thus allowing the rank of each commercial bank in terms of the incentives system rather on the performance of the productive process.
Assessing the moderating effect of subjective norm on luxury purchase intention: a study of Gen Y consumers in India
Authors: Jain Sheetal
Published: April 2020

Purpose

Although Generation Y consumers contribute significantly to the luxury market, still there is a limited amount of research conducted to explain their luxury consumption behavior, particularly in context of emerging markets like India. The main objectives of this study are to understand the key factors that affect luxury purchase intentions of Generation Y consumers using the theory of planned behavior (TPB) and to examine the moderating effect of subjective norm on other TPB variables, namely, attitude and perceived behavioral control.

Design/methodology/approach

Purposive sampling method was used to collect data from Generation Y luxury fashion consumers in New Delhi, India. Confirmatory factor analysis and structural equation modeling was employed to analyze the data.

Findings

The findings of this study revealed subjective norm and perceived behavioral control were positively related to luxury purchase intentions. Further, subjective norm was found to moderate the relationship between attitude and luxury purchase intentions.

Originality/value

This study will help consumer behavior researchers and practitioners to understand the core reason behind luxury purchase intentions of Generation Y consumers in India. It will enable luxury brand companies to create suitable marketing strategies which align with the mindset of this new demographic segment.
The relationship between Bitcoin returns, volatility and volume: asymmetric GARCH modeling
Authors: Sapuric Svetlana , Kokkinaki Angelika , Georgiou Ifigenia
Published: April 2020

Purpose

To show that when volume of trades is taken into consideration, Bitcoin does not seem as volatile as it claimed. Further, to study the relationship between Bitcoin trading volume, volatility and returns, and the asymmetry in response to economic information for the period from July 2010 to November 2017.

Design/methodology/approach

Comparison of Bitcoin price volatility with that of six currencies and gold. We repeat the analysis using returns divided by volume. We examine the relationship between volume, returns and volatility, and the asymmetry of the reaction of the volatility to economic news using asymmetric models (EGARCH) run for four meaningful distinct time periods/subsamples.

Findings

Positive and significant relationship between (1) volume and volatility after 2013 (year Bitcoin became popular) and (2) volume and returns before the Mt. Gox hack. During the euphoric period, starting at the beginning of 2013 until the Mt. Gox hack, unexpected increases in Bitcoin returns increased Bitcoin volatility more than unexpected, equally sized decreases (asymmetry).

Originality/value

We take into consideration the volume of trades to show that Bitcoin volatility seems high because of the low volume of trades. We study an extended time period, not covered by other studies. We divide our sample into four meaningful time periods based on important events in Bitcoin market history. This is important for a new market such as the Bitcoin market; the relationships under study are very important in markets where participants rely on technical analysis in the absence of reliable fundamental methodology to measure the intrinsic value of the asset.
People with dementia and carers online discussing surveillance
Authors: Vermeer Yvette , van Santen Joeke , Charlesworth Georgina , Higgs Paul
Published: April 2020

Purpose

This paper aims to interrogate online comments from consumers with dementia and family carers on surveillance technology products used by or for people with dementia.

Design/methodology/approach

A naturalistic, observational study of qualitative posts (N = 120) by people with dementia (n = 7) and family carers (n = 38) to discussion threads on surveillance technology (ST), hosted by an online dementia support forum in the Netherlands. Kozinet’s (2002) typology was used to describe respondent characteristics, and comments on features of ST products were analysed within a pre-existing framework.

Findings

Forum users were mainly “tourists” interested in ST, with some “insiders” interested in sharing experiences of ST use. They expressed a lack of trust in information from marketers and providers to the experience of being provided with poor information. Consumer-to-consumer comments on products triangulated with previous face-to-face qualitative studies. Carers prioritised “peace of mind” through location monitoring. In contrast, people with dementia prioritised user-friendliness (simple, with capability and compatible with daily routines).

Practical implications

Using online discussions of ST products provides a rapid approach to understanding current consumer needs and preferences in the ever-changing world of technology.

Originality/value

No previous study is known to have explored the views of carers and people with dementia in online discussions about ST.
Ethical practice in sharing and mining medical data
Authors: Watson Kevin , Payne Dinah M.
Published: April 2020

Purpose

The purpose of this paper is to review current practice in sharing and mining medical data revealing benefits, costs and ethical issues. Based on stakeholder perspectives and values, the authors create an ethical code to regulate the sharing and mining of medical information.

Design/methodology/approach

The framework is based on a review of academic, practitioner and legal research.

Findings

Owing to the inability of current safeguards to protect consumers from risks related to the disclosure of medical information, the authors develop a framework for ethical sharing and mining of medical data, security, transparency, respect, accountability, community and quality (STRACQ), which espouses security, transparency, respect, accountability, community and quality as the basic tenets of ethical data sharing and mining practice.

Research limitations/implications

The STRACQ framework is an original, previously unpublished contribution that will require modification over time based on discussion and debate within and among the academy, medical community and public policymakers.

Social implications

The framework for sharing borrows from the Fair Credit Reporting Act, allowing the collection and dissemination of identified medical data but placing strict limitations on use. Following this framework, benefits of shared and mined medical data are freely available with appropriate safeguards for consumer privacy.

Originality/value

Mandates for adoption of electronic health-care records require an understanding of medical data mining. This paper presents a review of data mining techniques and reasons for engaging in the practice of identifying benefits, costs and ethical issues. The authors create an original framework, STRACQ, for ethical sharing and mining of medical information, allowing knowledge exploration while protecting consumer privacy.