bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of CLV signalling in the negative regulation of mycorrhizal colonisation and nitrogen response of tomato
Authors: Wang Chenglei , Velandia Karen , Kwon Choon-Tak , Wulf Kate E. , Nichols David S. , Reid James B. , Foo Eloise
Published: July 2020

Plants form mutualistic nutrient acquiring symbioses with microbes, including arbuscular mycorrhizal fungi. The formation of these symbioses is costly and plants employ a negative feedback loop termed autoregulation of mycorrhizae (AOM) to limit arbuscular mycorrhizae (AM) formation. We provide evidence for the role of one leucine-rich-repeat receptor like kinase (FAB), a hydroxyprolineO-arabinosyltransferase enzyme (FIN) and additional evidence for one receptor like protein (SlCLV2) in the negative regulation of AM formation in tomato. Reciprocal grafting experiments suggest that theFABgene acts locally in the root, while theSlCLV2gene may act in both the root and the shoot. External nutrients including phosphate and nitrate can also strongly suppress AM formation. We found that FAB and FIN are required for nitrate suppression of AM but are not required for the powerful suppression of AM colonisation by phosphate. This parallels some of the roles of legume homologs in the autoregulation of the more recently evolved symbioses with nitrogen-fixing bacteria leading to nodulation. This deep homology in the symbiotic role of these genes suggests that in addition to the early signalling events that lead to the establishment of AM and nodulation, the autoregulation pathway might also be considered part of the common symbiotic toolkit that enabled plants to form beneficial symbioses.

Highlight

We describe the role of CLV signalling elements in the negative regulation of arbuscular mycorrhizal symbioses of tomato, including influencing nitrate but not phosphate suppression of mycorrhizal colonisation.
Demonstration of electron diffraction from membrane protein crystals grown in a lipidic mesophase after lamella preparation by focused ion beam milling at cryogenic temperatures
Authors: Polovinkin Vitaly , Khakurel Krishna , Babiak Michal , Angelov Borislav , Schneider Bohdan , Dohnalek Jan , Andreasson Jakob , Hajdu Janos
Published: July 2020

Electron crystallography of sub-micron sized 3D protein crystals has emerged recently as a valuable field of structural biology.In mesocrystallization methods, utilizing lipidic mesophases, particularly lipidic cubic phases (LCPs), can produce high-quality 3D crystals of membrane proteins (MPs). A major step towards realising 3D electron crystallography of MP crystals, grownin meso, is to demonstrate electron diffraction from such crystals. The first task is to remove the viscous and sticky lipidic matrix, surrounding the crystals without damaging the crystals. Additionally, the crystals have to be thin enough to let electrons traverse them without significant multiple scattering. In the present work, we experimentally verified the concept that focused ion beam milling at cryogenic temperatures (cryo-FIB) can be used to remove excess host lipidic mesophase matrix, and then thin the crystals to a thickness suitable for electron diffraction. In this study, bacteriorhodopsin (BR) crystals grown in a lipidic mesophase of monoolein were used as a model system. LCP from a part of a 50-μm thick crystal, which was flash-frozen in liquid nitrogen, was milled away with a gallium FIB under cryogenic conditions, and a part of the crystal itself was thinned into a ∼210-nm thick lamella with the ion beam. The frozen sample was then transferred into an electron cryo-microscope (cryo-EM), and a nanovolume of ∼1400×1400×210 nm3of the BR lamella was exposed to 200-kV electrons at a fluence of ∼0.06 e−/Å2. The resulting electron diffraction peaks were detected beyond 2.7-Å resolution (with mean signal-to-noise ratio  of >7) by a CMOS-based Ceta 16M camera. The results demonstrate, that cryo-FIB milling produces high quality lamellae from crystals grown in lipidic mesophases, and pave the way for 3D electron crystallography on crystals grown or embedded in highly viscous media.

Synopsis

Electron diffraction experiments on crystals of membrane proteins grown in lipidic mesophases have not been possible due to a thick layer of viscous crystallisation medium around the crystals. Here we show that focused ion beam milling at cryogenic temperatures (cryo-FIB milling) can remove the viscous layer, and demonstrate high-quality electron diffraction on a FIB-milled lamella of a bacteriorhodopsin 3D crystal.
Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine co-varies with risk factors for Parkinson’s
Authors: Brimblecombe Katherine R. , Connor-Robson Natalie , Bataille Carole J. R. , Roberts Bradley M. , Gracie Caitlin , O’Connor Bethan , te Water Naude Rebecca , Karthik Gayathri , Russell Angela J. , Wade-Martins Richard , Cragg Stephanie J.
Published: July 2020

Ca2+entry into nigrostriatal dopamine (DA) neurons and axons via L-type voltage-gated Ca2+channels (LTCCs) contributes respectively to pacemaker activity and DA release, and has long been thought to contribute to vulnerability to degeneration in Parkinson’s disease. LTCC function is greater in DA axons and neurons from substantia nigra pars compacta than from ventral tegmental area, but this is not explained by channel expression level. We tested the hypothesis that LTCC-control of DA release is governed rather by local mechanisms, focussing on candidate biological factors known to operate differently between types of DA neurons and/or be associated with their differing vulnerability to parkinsonism, including biological sex, α-synuclein, DA transporters (DATs), and calbindin-D28k (Calb1). We detected evoked DA releaseex vivoin mouse striatal slices using fast-scan cyclic voltammetry, and assessed LTCC support of DA release by detecting the inhibition of DA release by the LTCC inhibitors isradipine or CP8. Using genetic knockouts or pharmacological manipulations we identified that striatal LTCC support of DA release depended on multiple intersecting factors, in a regionally and sexually divergent manner. LTCC function was promoted by factors associated with Parkinsonian risk, including male sex, α-synuclein, DAT, and a dorsolateral co-ordinate, but limited by factors associated with protection i.e. female sex, glucocerebrosidase activity, Calb1, and ventromedial co-ordinate. Together, these data show that LTCC function in DA axons, and isradipine effect, are locally governed and suggest they vary in a manner that in turn might impact on, or reflect, the cellular stress that leads to parkinsonian degeneration.

Abstract Figure
Detecting oncogenic selection through biased allele retention in The Cancer Genome Atlas
Authors: Luft Juliet , Young Robert S. , Meynert Alison M. , Taylor Martin S.
Published: July 2020

Background

The loss of genetic diversity in segments over a genome (loss-of-heterozygosity, LOH) is a common occurrence in many types of cancer. By analysing patterns of preferential allelic retention during LOH in approximately 10,000 cancer samples from The Cancer Genome Atlas (TCGA), we sought to systematically identify genetic polymorphisms currently segregating in the human population that are preferentially selected for, or against during cancer development.

Results

Experimental batch effects and cross-sample contamination were found to be substantial confounders in this widely used and well studied dataset. To mitigate these we developed a generally applicable classifier (GenomeArtiFinder) to quantify contamination and other abnormalities. We provide these results as a resource to aid further analysis of TCGA whole exome sequencing data. In total, 1,678 pairs of samples (14.7%) were found to be contaminated or affected by systematic experimental error. After filtering, our analysis of LOH revealed an overall trend for biased retention of cancer-associated risk alleles previously identified by genome wide association studies. Analysis of predicted damaging germline variants identified highly significant oncogenic selection for recessive tumour suppressor alleles. These are enriched for biological pathways involved in genome maintenance and stability.

Conclusions

Our results identified predicted damaging germline variants in genes responsible for the repair of DNA strand breaks and homologous repair as the most common targets of allele biased LOH. This suggests a ratchet-like process where heterozygous germline mutations in these genes reduce the efficacy of DNA double-strand break repair, increasing the likelihood of a second hit at the locus removing the wild-type allele and triggering an oncogenic mutator phenotype.
RNAxplorer: Harnessing the Power of Guiding Potentials to Sample RNA Landscapes
Authors: Entzian Gregor , Hofacker Ivo , Ponty Yann , Lorenz Ronny , Tanzer Andrea
Published: July 2020

Motivation

Predicting the folding dynamics of RNAs is a computationally difficult problem, first and foremost due to the combinatorial explosion of alternative structures in the folding space. Abstractions are therefore needed to simplify downstream analyses, and thus make them computationally tractable. This can be achieved by various structure sampling algorithms. However, current sampling methods are still time consuming and frequently fail to represent key elements of the folding space.

Method

We introduceRNAxplorer, a novel adaptive sampling method to efficiently explore the structure space of RNAs.RNAxploreruses dynamic programming to perform an efficient Boltzmann sampling in the presence of guiding potentials, which are accumulated into pseudo-energy terms and reflect similarity to already well-sampled structures. This way, we effectively steer sampling towards underrepresented or unexplored regions of the structure space.

Results

We developed and applied different measures to benchmark our sampling methods against its competitors. Most of the measures show thatRNAxplorerproduces more diverse structure samples, yields rare conformations that may be inaccessible to other sampling methods and is better at finding the most relevant kinetic traps in the landscape. Thus, it produces a more representative coarse graining of the landscape, which is well suited to subsequently compute better approximations of RNA folding kinetics.

Availability

https://github.com/ViennaRNA/RNAxplorer/

Contact

andrea.tanzer@meduniwien.ac.at,ronny@tbi.univie.ac.at
Synergy between Wsp1 and Dip1 may initiate assembly of endocytic actin networks
Authors: Balzer Connor J. , James Michael L. , Helgeson Luke A. , Sirotkin Vladimir , Nolen Brad J.
Published: July 2020

The actin filament nucleator Arp2/3 complex is activated at cortical sites inS. pombeto assemble branched actin networks that drive endocytosis. Arp2/3 complex activators Wsp1 and Dip1 are required for proper actin assembly at endocytic sites, but how they coordinately control Arp2/3-mediated actin assembly is unknown. Alone, Dip1 activates Arp2/3 complex without preexisting actin filaments to nucleate “seed” filaments that activate Wsp1-bound Arp2/3 complex, thereby initiating branched actin network assembly. In contrast, because Wsp1 requires pre-existing filaments to activate, it has been assumed to function exclusively in propagating actin networks by stimulating branching from pre-existing filaments. Here we show that Wsp1 is important not only for propagation, but also for initiation of endocytic actin networks. Using single molecule TIRF microscopy we show that Wsp1 synergizes with Dip1 to co-activate Arp2/3 complex. Synergistic coactivation does not require pre-existing actin filaments, explaining how Wsp1 contributes to actin network initiation in cells.
Comparison of two commercial platforms and a laboratory developed test for detection of SARS-CoV-2 RNA
Authors: Mannonen Laura , Kallio-Kokko Hannimari , Loginov Raisa , Jääskeläinen Anu , Jokela Pia , Antikainen Jenni , Väre Paula , Kekäläinen Eliisa , Kurkela Satu , Jarva Hanna , Lappalainen Maija
Published: July 2020

Mitigation of the ongoing COVID-19 pandemic requires reliable and accessible laboratory diagnostic services. We evaluated the performance of one LDT and two commercial tests, cobas® SARS-CoV-2 (Roche) and Amplidiag® COVID-19 (Mobidiag), for the detection of SARS-CoV-2 RNA in respiratory specimens. 183 specimens collected from suspected COVID-19 patients were studied with all three methods to compare their performance. In relation to the reference standard, which was established as the result obtained by two of the three studied methods, the positive percent agreement (PPA) was highest for cobas® test (100%), followed by Amplidiag® test and the LDT (98.9%). The negative percent agreement (NPA) was lowest for cobas® test (89.4%), followed by Amplidiag® test (98.8%) and the highest value was obtained for LDT (100%). The dilution series conducted for specimens, however, suggests significantly higher sensitivity for the cobas® assay in comparison with the other two assays and the low NPA value may be due to the same reason. In general, all tested assays performed adequately. Both the time from sample to result and hands-on time per sample were shortest for cobas® test. Clinical laboratories need to be prepared for uninterrupted high-throughput testing during the coming months in mitigation of the pandemic. To secure that, it is of critical importance for clinical laboratories to maintain several simultaneous platforms in their SARS-CoV-2 nucleic acid testing.
Identifying regions for enhanced control of gambiense sleeping sickness in the Democratic Republic of Congo
Authors: Huang Ching-I , Crump Ronald E , Brown Paul E , Spencer Simon E F , Miaka Erick Mwamba , Shampa Chansy , Keeling Matt J , Rock Kat S
Published: July 2020

Gambiense human African trypanosomiasis (sleeping sickness, gHAT) is a disease targeted for elimination of transmission (EOT) by 2030. Despite the number of new cases reported annually being at a historical minimum, the likelihood of achieving EOT is unknown. We utilised modelling to study the impact of four strategies comprised of currently-available intervention methods including active and passive screening and vector control (VC) on transmission across 168 health zones in the Democratic Republic of the Congo. By estimating the median year of EOT and the probability of EOT by 2030 under each strategy, the model predicts only 81 health zones are on track to achieve the EOT target using medical-only strategies and this number drops to 52 when uncertainty is considered (> 90% probability). Although all health zones are predicted to meet EOT by 2030 under strategies with VC, blanket coverage is impractical so this analysis provides a priority list of health zones for consideration for supplementary VC implementation in conjunction with medical interventions.
Structural Barriers to Green and Blue Spaces: A Scoping Review Protocol
Authors: Nejade Rachel M. , Grace Daniel M. , Bowman Leigh R.
Published: July 2020

Background

Emerging evidence has demonstrated that nature-based interventions (NBIs) can improve mental and physical health. Considering that the global burden of poor mental health continues to rise, such interventions could be a cost-effective means to improve mental health, as well as reconnect individuals with the natural world, and thus aid efforts. However, the effectiveness of NBIs as a prescriptive intervention is, in part, a function of access to blue and green spaces. Accordingly, this scoping review will explore how structural inequalities influence the effectiveness of nature-based interventions as treatment options for mental and physical ill health.

Methods

A scoping review will be conducted to identify the barriers and facilitators associated with the utilisation of green and blue spaces. The review will follow the PRISMA-ScR guidelines, in addition to the associated Cochrane guidelines for scoping reviews. A literature search will be performed across five databases, and articles will be selected based on key inclusion/ exclusion criteria. All data will be extracted to a pre-defined charting table. The primary and secondary outcomes will be mental and physical health respectively.

Discussion

This review will better inform relevant stakeholders of the potential enablers and barriers of nature-based interventions, and thereby improve provision and implementation of NBIs as public health initiatives.

Ethics and Dissemination

All data rely on secondary, publicly available data sources; therefore no ethical clearance is required.

Upon completion, the results of this study will be disseminated via the Imperial College London Community and published in an open access, peer-reviewed journal.

Article Summary

Strengths and Limitations of this Study

This scoping review protocol is the first to focus on the accessibility to green and blue spaces in the context of mental and physical health.

This protocol and subsequent review benefit from increased transparency, a systematised strategy (PRISMA-ScR), and a reduction in the risk of bias, through publication in an open access journal.

This review will also capture grey literature - studies published outside peer-reviewed journals.

Due to the broad nature of the review, the research may unearth more questions than solutions.

Registration Number

Open Science Framework: 10.17605/OSF.IO/8J5Q3
Cognitive Benefits of Exercise Interventions: An fMRI Activation Likelihood Estimation Meta-Analysis
Authors: Yu Qian , Herold Fabian , Becker Benjamin , KluGah-Brown Ben , Zhang Yanjie , Perrey Stephane , Veronese Nicola , Müller Notger G. , Zou Liye , Kramer Arthur F.
Published: July 2020

Despite a growing number of functional MRI studies reporting exercise-induced changes during cognitive processing, a systematic determination of the underlying neurobiological pathways is currently lacking. To this end, our neuroimaging meta-analysis included 20 studies and investigated the influence of exercise on cognition-related functional brain activation. The overall meta-analysis encompassing all experiments revealed exercise-induced changes in the left parietal lobe during cognitive processing. Subgroup analysis further revealed that in the younger-age group (<35 years old) exercise induced more widespread changes in the right hemisphere whereas in the older-age group (≥35 years old) exercise-induced changes were restricted to the left parietal lobe. Furthermore, subgroup analysis for exercise intervention duration, showed that shorter exercise interventions induced changes in regions connected with frontoparietal and default mode networks whereas regions exhibiting effects of longer interventions connected with frontoparietal and dorsal attention networks. Our findings suggest that physical exercise training leads to changes in functional activation patterns primarily located in precuneus and associated with frontoparietal, dorsal attention and default mode networks. Furthermore, exercise-induced changes in functional brain activation varied as a function of age and exercise intervention duration.
Snapshot of the evolution and mutation patterns of SARS-CoV-2
Authors: Zhao Jin , Sun Jiumeng , He Wan-Ting , Ji Xiang , Gao Qi , Zhai Xiaofeng , Suchard Marc A. , Hong Samuel L. , Baele Guy , Su Shuo , Zhou Jiyong , Veit Michael
Published: July 2020

The COVID-19 pandemic is the most important public health threat in recent history. Here we study how its causal agent, SARS-CoV-2, has diversified genetically since its first emergence in December 2019. We have created a pipeline combining both phylogenetic and structural analysis to identify possible human-adaptation related mutations in a data set consisting of 4,894 SARS-CoV-2 complete genome sequences. Although the phylogenetic diversity of SARS-CoV-2 is low, the whole genome phylogenetic tree can be divided into five clusters/clades based on the tree topology and clustering of specific mutations, but its branches exhibit low genetic distance and bootstrap support values. We also identified 11 residues that are high-frequency substitutions, with four of them currently showing some signal for potential positive selection. These fast-evolving sites are in the non-structural proteins nsp2, nsp5 (3CL-protease), nsp6, nsp12 (polymerase) and nsp13 (helicase), in accessory proteins (ORF3a, ORF8) and in the structural proteins N and S. Temporal and spatial analysis of these potentially adaptive mutations revealed that the incidence of some of these sites was declining after having reached an (often local) peak, whereas the frequency of other sites is continually increasing and now exhibit a worldwide distribution. Structural analysis revealed that the mutations are located on the surface of the proteins that modulate biochemical properties. We speculate that this improves binding to cellular proteins and hence represents fine-tuning of adaptation to human cells. Our study has implications for the design of biochemical and clinical experiments to assess whether important properties of SARS-CoV-2 have changed during the epidemic.
A County-Level Susceptibility Index and Coronavirus Disease 2019 Mortality in the United States: A Socioecological Study
Authors: Khan Sadiya S. , McCabe Megan E. , Krefman Amy E. , Petito Lucia C. , Yang Xiaoyun , Kershaw Kiarri N. , Pool Lindsay , Allen Norrina B.
Published: July 2020

As of June 2020, the United States (US) has experienced the highest number of deaths related to coronavirus disease 2019 (Covid-19) in the world, but significant geographic heterogeneity exists at the county-level. Therefore, we sought to classify counties in the United States across multiple domains utilizing a socioecological framework and examine the association between these county-level groups and Covid-19 mortality. We harmonized and linked county-level sociodemographic, health, and environmental metrics associated with increased susceptibility for Covid-19 mortality. Latent class analysis defined a county-level susceptibility index (CSI) based on these metrics (n=2701 counties). Next, we used linear regression models to estimate the associations of the CSI and Covid-19 deaths per capita and initial mortality doubling time (as of 6/2/20), adjusted for days since first Covid-19 case. We identified 4 groups classified by the CSI with distinct sociodemographic, health, and environmental profiles and widespread geographic dispersion. Covid-19 deaths per capita were significantly higher in the group consisting of rural, vulnerable counties (55.8 [95% CI 50.3-61.2] deaths per 100,000) compared with the group with diverse, urban counties (32.2 [27.3-37.0]) at similar points in the outbreak (76 days since first case). Our findings can inform equitable resource allocation for Covid-19 to allow targeted public health preparedness and response in vulnerable counties.
Wearable Respiration Monitoring: Interpretable Inference with Context and Sensor Biomarkers
Authors: Alam Ridwan , Peden David B. , Lach John C.
Published: July 2020

Breathing rate (BR), minute ventilation (VE), and other respiratory parameters are essential for real-time patient monitoring in many acute health conditions, such as asthma. The clinical standard for measuring respiration, namely Spirometry, is hardly suitable for continuous use. Wearables can track many physiological signals, like ECG and motion, yet not respiration. Deriving respiration from other modalities has become an area of active research. In this work, we infer respiratory parameters from wearable ECG and wrist motion signals. We propose a modular and generalizable classification-regression pipeline to utilize available context information, such as physical activity, in learning context-conditioned inference models. Morphological and power domain novel features from the wearable ECG are extracted to use with these models. Exploratory feature selection methods are incorporated in this pipeline to discover application-specific interpretable biomarkers. Using data from 15 subjects, we evaluate two implementations of the proposed pipeline: for inferring BR and VE. Each implementation compares generalized linear model, random forest, support vector machine, Gaussian process regression, and neighborhood component analysis as contextual regression models. Permutation, regularization, and relevance determination methods are used to rank the ECG features to identify robust ECG biomarkers across models and activities. This work demonstrates the potential of wearable sensors not only in continuous monitoring, but also in designing biomarker-driven preventive measures.
Symbiont-mediated fly survival is independent of defensive symbiont genotype in the Drosophila melanogaster-Spiroplasma-wasp interaction
Authors: Jones Jordan E. , Hurst Gregory D. D.
Published: July 2020

When a parasite attacks an insect, the outcome is commonly modulated by the presence of defensive heritable symbionts residing within the insect host. Previous studies noted markedly different strengths of Spiroplasma-mediated fly survival following attack by the same strain of wasp. One difference between the two studies was the strain of Spiroplasma used. We therefore performed a common garden laboratory experiment to assess whether Spiroplasma-mediated protection depends upon the strain of Spiroplasma. We perform this analysis using the two strains of male-killing Spiroplasma used previously, and examined response to challenge by two strains of Leptopilina boulardi and two strains of Leptopilina heterotoma wasp. We found no evidence Spiroplasma strain affected fly survival following wasp attack. In contrast, analysis of the overall level of protection, including the fecundity of survivors of wasp attack, did indicate the two Spiroplasma strains tested varied in protective efficiency against three of the four wasp strains tested. These data highlight the sensitivity of symbiont-mediated protection phenotypes to laboratory conditions, and the importance of common garden comparison. Our results also indicate that Spiroplasma strains can vary in protective capacity in Drosophila, but these differences may exist in the relative performance of survivors of wasp attack, rather than in survival of attack per se.
Predicting base editing outcomes with an attention-based deep learning algorithm trained on high-throughput target library screens
Authors: Marquart Kim F. , Allam Ahmed , Janjuha Sharan , Sintsova Anna , Villiger Lukas , Frey Nina , Krauthammer Michael , Schwank Gerald
Published: July 2020

Base editors are chimeric ribonucleoprotein complexes consisting of a DNA-targeting CRISPR-Cas module and a single-stranded DNA deaminase. They enable conversion of C•G into T•A base pairs and vice versa on genomic DNA. While base editors have vast potential as genome editing tools for basic research and gene therapy, their application has been hampered by a broad variation in editing efficiencies on different genomic loci. Here we perform an extensive analysis of adenine- and cytosine base editors on thousands of lentivirally integrated genetic sequences and establish BE-DICT, an attention-based deep learning algorithm capable of predicting base editing outcomes with high accuracy. BE-DICT is a versatile tool that in principle can be trained on any novel base editor variant, facilitating the application of base editing for research and therapy.
Nitrergic neurons of the forepaw representation in the somatosensory and motor cortices
Authors: Guimaraes Bárbara de Paula P. F. , Curado Marco R. , Nogueira-Campos Anaelli Aparecida , Houzel Jean Christophe , Gattass Ricardo
Published: July 2020

Nitrergic neurons (NN) are inhibitory neurons capable of releasing nitric oxide (NO) that are labeled with NADPHd histochemistry, allowing the study of their distribution and morphology. The rat primary somatosensory (S1) and motor (M1) cortices are a favorable model to investigate the morphology of the NN population. The distribution of the type I NN of the forepaw representation in the primary somatosensory (S1) and motor (M1) cortices of the rat in different laminar compartments and the morphological parameters related to the cell body and dendritic arborization were measured and compared. We found that the neuronal density in the S1 (130 NN/mm3) was higher than in the M1 (119 NN/mm3). Most NN neurons are multipolar (S1 with 58%; M1 with 69%) and a minority are horizontal (S1 with 6%; M1 with 12%). NN found in the S1 had a higher verticality index than those of the M1, and no statistical differences was found for the others morphological parameters. We also demonstrated statistical differences for most of the morphological parameters of the NN between different cortical compartments of the S1 and M1. Our results indicate that the NN of the forepaw in the S1 and M1 correspond to a single neuronal population whose functionality is independent of the different types of sensory and motor processing. However, the morphological differences found between cortical compartments of S1 and M1, as well as the higher density of NN found in the S1 indicate that the release of NO varies along and between the areas.
Cell type-specific weighting-factors to solve solid organs-specific limitations of single cell RNA-sequencing
Authors: Tejima Kengo , Kozawa Satoshi , Sato Thomas N.
Published: July 2020

While single-cell RNA-sequencing (scRNA-seq) is a popular method to analyze gene expression and cellular composition at single-cell resolution, it harbors shortcomings: The failure to account for cell-to-cell variations of transcriptome-size (i.e., the total number of transcripts per cell) and also cell dissociation/processing-induced cryptic gene expression. This is particularly a problem when analyzing highly heterogeneous solid tissues/organs, which requires cell dissociation for the analysis. As a result, there exists a discrepancy between bulk RNA-seq result and virtually reconstituted bulk RNA-seq result using its composite scRNA-seq data. To fix this problem, we propose a computationally calculated coefficient, “cell type-specific weighting-factor (cWF)”. Here, we introduce a concept and a method of its computation and report cWFs for 76 cell-types across 10 solid organs. Their fidelity is validated by more accurate reconstitution and deconvolution of bulk RNA-seq data of diverse solid organs using the scRNA-seq data and the cWFs of their composite cells. Furthermore, we also show that cWFs effectively predict aging-progression, implicating their diagnostic applications and also their association with aging mechanism. Our study provides an important method to solve critical limitations of scRNA-seq analysis of complex solid tissues/organs. Furthermore, our findings suggest a diagnostic utility and biological significance of cWFs.
Circuit-free, optoelectronic sensing of electrodermal activities based on photon recycling of a micro-LED
Authors: Ding He , Lv Guoqing , Shi Zhao , Cheng Dali , Huang Yunxiang , Yin Lan , Yang Jian , Wang YongTian , Sheng Xing
Published: July 2020

Conventional epidermal electronics integrate multiple power harvesting, signal amplification and data transmission components for wireless biophysical and biochemical signal detection. This paper reports the real-time electrodermal activities can be optically captured using a microscale light-emitting diode (micro-LED), eliminating the need for complicated sensing circuit. Owing to its strong photon-recycling effects, the micro-LED’s photoluminescence (PL) emission exhibits a superlinear dependence on the external resistance. Taking advantage of this unique mechanism, the galvanic skin response (GSR) of a human subject is optically monitored, and it demonstrates that such an optoelectronic sensing technique outperforms a traditional tethered, electrically based GSR sensing circuit, in terms of its footprint, accuracy and sensitivity. This presented optoelectronic sensing approach could establish promising routes to advanced biological sensors.
Genetic background modifies vulnerability to glaucoma related phenotypes inLmx1bmutant mice
Authors: Tolman NG , Macalinao DG , Kearney AL , MacNicoll KH , Montgomery CL , de Vries WN , Jackson IJ , Cross SH , Kizhatil K , Nair KS , John SWM
Published: July 2020

Variants in the LIM homeobox transcription factor 1-beta gene (LMX1B) predispose individuals to elevated intraocular pressure (IOP), a key risk factor for glaucoma. However, the effect ofLMX1Bmutations varies widely between individuals. To better understand mechanisms underlying LMX1B-related phenotypes and individual differences, we backcrossed theLmx1bV265D(also known asLmx1bIcst) allele onto the C57BL/6J (B6), 129/Sj (129), C3A/BLiA-Pde6b+/J (C3H), and DBA/2J-Gpnmb+(D2-G) strain backgrounds. Strain background had a significant effect on the onset and severity of ocular phenotypes inLmx1bV265D/+mutant mice. Mice of the B6 background were the most susceptible to developing elevated IOP, severe anterior segment developmental anomalies (including malformed eccentric pupils, iridocorneal strands, and corneal abnormalities) and glaucomatous nerve damage. In contrast,Lmx1bV265Dmice of the 129 background were the most resistant to developing anterior segment abnormalities, had less severe IOP elevation than B6 mutants at young ages, and showed no detectable nerve damage. To identify genetic modifiers of susceptibility toLmx1bV265D-induced glaucoma-associated phenotypes, we performed a mapping cross between mice of the B6 (susceptible) and 129 (resistant) backgrounds. We identified a modifier locus on Chromosome 18, with the 129 allele(s) substantially lessening severity of ocular phenotypes, as confirmed by congenic analysis. By demonstrating a clear effect of genetic background in modulatingLmx1b-induced phenotypes, by providing a panel of strains with different phenotypic severities and by identifying a modifier locus, this study lays a foundation for better understanding the roles of LMX1B in glaucoma with the goal of developing new treatments.
Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions
Authors: Bodzęta Anna , Berger Florian , MacGillavry Harold D.
Published: July 2020

Presynaptic metabotropic glutamate receptors (mGluRs) are essential for activity-dependent modulation of synaptic transmission. However, the mechanisms that control the subsynaptic dynamics of these receptors and their contribution to synaptic signaling are poorly understood. Here, using complementary super-resolution microscopy and single-molecule tracking techniques, we provide novel insights into the molecular mechanisms that control the nanoscale distribution and mobility of presynaptic mGluRs in hippocampal neurons. We demonstrate that the group II receptor mGluR2 localizes diffusely along the axon and boutons, and is highly mobile, while the group III receptor mGluR7 is stably anchored at the active zone, indicating that distinct mechanisms underlie the dynamic distribution of these receptor types. Surprisingly, using domain swapping experiments we found that intracellular interactions modulate surface diffusion of mGluR2, but not mGluR7. Instead, we found that immobilization of mGluR7 at the active zone relies on its extracellular domain. Importantly, receptor activation or increase in synaptic activity did not alter the surface mobility of presynaptic mGluRs. Finally, computational modeling of presynaptic mGluR activity revealed that the precise subsynaptic distribution of mGluRs controls their activation probability and thus directly impacts their ability to modulate neurotransmitter release. Altogether, this study demonstrates that distinct mechanisms control surface mobility of presynaptic mGluRs to differentially contribute to the regulation of glutamatergic synaptic transmission.
A long-read RNA-seq approach to identify novel transcripts of very large genes
Authors: Uapinyoying Prech , Goecks Jeremy , Knoblach Susan M. , Panchapakesan Karuna , Bonnemann Carsten G. , Partridge Terence A. , Jaiswal Jyoti K. , Hoffman Eric P.
Published: July 2020

RNA-seq is widely used for studying gene expression, but commonly used sequencing platforms produce short reads that only span up to two exon junctions per read. This makes it difficult to accurately determine the composition and phasing of exons within transcripts. Although long-read sequencing improves this issue, it is not amenable to precise quantitation, which limits its utility for differential expression studies. We used long-read isoform sequencing combined with a novel analysis approach to compare alternative splicing of large, repetitive structural genes in muscles. Analysis of muscle structural genes that produce medium (Nrap: 5 kb), large (Neb: 22 kb), and very large (Ttn: 106 kb) transcripts in cardiac muscle, and fast and slow skeletal muscles identified unannotated exons for each of these ubiquitous muscle genes. This also identified differential exon usage and phasing for these genes between the different muscle types. By mapping the in-phase transcript structures to known annotations, we also identified and quantified previously unannotated transcripts. Results were confirmed by endpoint PCR and Sanger sequencing, which revealed muscle-type-specific differential expression of these novel transcripts. The improved transcript identification and quantification shown by our approach removes previous impediments to studies aimed at quantitative differential expression of ultralong transcripts.
Solvent-assisted planar structure of a stilbene-based salicylhydrazone compound: crystal structure, solvent- and aggregation-induced emission, and switchable luminescence colouration
Authors: Fang Zong-Bin , Zhang Bin , Yang Qi-Zheng , Zheng Wenxu , Hu Xiao-Lin , Huang Xi-He , Huang Chang-Cang , Zhuang Nai-Feng , Wu Shu-Ting
Published: July 2020

A novel stilbene-based salicylhydrazone compound {systematic name: (E)-4,4′-(ethene-1,2-diyl)bis[(N′E)-N′-(2-hydroxybenzylidene)benzohydrazide] dimethyl sulfoxide disolvate, C30H24N4O4·2C2H6OS or L·2DMSO} was synthesized and characterized by single-crystal X-ray diffraction, powder X-ray diffraction and luminescence spectroscopy. The title compound crystallizes in the monoclinic space group P21/c, with half a symmetry-independent L molecule and one dimethyl sulfoxide (DMSO) solvent molecule in the asymmetric unit. The L molecule adopts an almost planar structure, with a small dihedral angle between the planes of the stilbene and salicylhydrazone groups. There are multiple π–π stacking interactions between adjacent L molecules. The DMSO solvent molecules act as proton donors and acceptors, forming hydrogen bonds of various strengths with the L molecules. In addition, the geometry optimization of a single molecule of L and its luminescence properties either in solution, as a solvated solid or as a desolvated solid were studied. The compound shows an aggregation-induced emission (AIE) effect and exhibits switchable luminescence colouration in the solid state by the simple removal or re-addition of the DMSO solvent.
Analyzing the Lean Six Sigma enabled organizational performance to enhance operational efficiency
Authors: Raval Shruti J. , Kant Ravi , Shankar Ravi
Published: July 2020

Purpose

The aim of this analysis is to review the Indian manufacturing organizations practicing Lean Six Sigma (LSS) tools/techniques with an objective of monitoring the performance of an organization and to develop recommendation for strategies to benchmark organizational operational efficiency.

Design/methodology/approach

This study offers insights of the LSS performance measurement aspects of the Indian manufacturing organizations based on Data envelopment analysis (DEA) approach. The five inputs and two outputs are considered on the basis of literature review and discussed with the practitioners.

Findings

In this analysis, the relative efficiency score of 18 Indian manufacturing organizations has been determined in order to assist evaluation of the impact of monetary investment on the outputs. The present analysis not only investigates the optimum level of input variables but also lays down a significant observation that an organization having higher profit and inventory turnover ratio is not necessarily an efficient organization.

Practical implications

The results assist to determine the best practice units, potential source of inefficiency and deliver beneficial data for the consistent enhancement of the operational efficiency. The DEA results assist managers and decision makers to derive appropriate strategies to enhance their performance with reference to the efficient organization and to regard it as their role model.

Originality/value

This analysis renders a DEA based framework of LSS practicing Indian manufacturing organizations. The framework is unique in terms of its input-outputs variable selection and measurement procedure.
Towards a framework for public relations practice in the financial services sector of Ghana
Authors: Anani-Bossman Albert , Mudzanani Takalani Eric
Published: July 2020

Purpose

The goal of the study is to develop an integrated, non-sequential framework for excellent public relations management for the financial services sector in Ghana. The study empirically analyzes how PR is conceptualized and practiced in relation to the purpose (models) and roles (activities).

Design/methodology/approach

The study adopted the qualitative in-depth interview approach to gauge the views of 22 PR practitioners.

Findings

Practitioners of most communication departments have no PR background, and this influenced their conceptualization of PR. Essentially, PR in Ghana is shaped, to a large extent, by a western ideology. PR is however influenced greatly by strong interpersonal relationships, which is premised largely on the culture of the country. What is obvious is that PR in the financial services sector is not fully strategic. Although practitioners occupy managerial roles, they are limited in their ability to make impact due a lack of understanding by management about the purpose of PR and budgetary constraints.

Research limitations/implications

The use of a qualitative approach means the result cannot be generalized. As the study focussed on one sector, it will be essential to look at other sectors using a generalized sample.

Originality/value

The study developed an integrative non-sequential PR framework based on literature and empirical findings. The framework differs in certain aspects from some of the recommendations made by literature for an excellent PR practice.
Who networks? – A meta-analysis of networking and personality
Authors: Bendella Hadjira , Wolff Hans-Georg
Published: July 2020

Purpose

Networking refers to goal-directed behaviors focused on building and cultivating informal relationships to obtain career-related resources. According to Gibson et al.'s (2014) model, personality traits represent prominent and important antecedents of networking. This study seeks to provide robust evidence on relationships between personality and networking by summarizing prior research using meta-analytical tools.

Design/methodology/approach

The authors classify linking attributes between networking and personality into social, idea-related, task-related and affective behavioral domains and additionally include three compound traits that relate to several domains. They investigate two potential moderators: internal vs. external networking and prominent networking measures. Their comprehensive literature search identified 41 studies with 46 independent samples.

Findings

The authors find that social, idea-related and task-related traits have positive relationships with networking of medium effect size, whereas affective traits exhibit small but significantly positive effects. The compound trait of proactive personality appears to be the best predictor of networking. Moderator analyses indicate that there were hardly any differences concerning internal and external networking and also prominent measures.

Originality/value

The present study goes beyond narrative reviews contributing the first quantitative summary of these relationships. It identifies four behavioral domains that represent characteristics relevant to networking. The findings largely corroborate, but at times correct, narrative reviews on dispositional antecedents of networking. The authors highlight the importance of compound traits that have yet been overlooked by narrative reviews (e.g. self-monitoring).
Are organizations committed to stress management interventions?
Authors: Molek-Winiarska Dorota , Molek-Kozakowska Katarzyna
Published: July 2020

Purpose

Work-related stress causes individual, societal and economic costs. Stress management interventions (SMIs) are implemented to decrease those costs, reduce the psychosocial harms and increase workers' productivity. This article reports on a study of a substantial sample of enterprises to verify what types of SMIs they implemented and how they assessed the results of these interventions.

Design/methodology/approach

Specially designed surveys were collected in 2015–2017 from 408 organizations of different sizes and sectors in Poland, including multinationals. The reliability of the questionnaire was satisfactory (Cr. 0.84).

Findings

Results show that 59% of enterprises are aware of SMIs but only about 30% implemented one within the last three years. The implementations usually covered both organizational and individual-level interventions. The assessment of SMI effectiveness was conducted in just about one-third of the organizations and was based on estimations of the levels and sources of stress. Hardly any companies compared economic and psychosocial costs of stress before and after SMIs.

Research limitations/implications

The most important recommendation from this study is to increase the awareness of causes of stress among managing directors. Also, organizations and HR staff need more assistance from specialists who know how to measure and help reduce work stress.

Originality/value

The literature on stress interventions at work usually focusses on their psychological effects. This paper explores the organizational perspective and the commitment to implement the interventions in companies.
Creating conditions for sustainable degree apprenticeships in England
Authors: Lester Stan
Published: July 2020

Purpose

The purpose of this paper is to report on a study funded by the Edge Foundation, an independent educational charity, to investigate what is needed in order for English higher education to operate degree apprenticeships (DAs) on a sustainable basis.

Design/methodology/approach

The study, conducted in 2019–2020, took the form of a literature review, semi-structured interviews with employers, institutional staff members and apprentices in three fields, and an open online survey.

Findings

This study illustrates a high level of support for DAs amongst those who are involved in them, whether as educators, employers or apprentices. Degree Apprenticeships aid public-sector recruitment, support progression routes and social mobility within the existing workforce, and contribute to recruitment and productivity in public services and economically critical industries. Practices in the organisation and delivery of apprenticeships are variable, but a clear need is illustrated for strong institution–employer partnerships, integration between on- and off-the-job learning, expansive workplace learning environments, and co-ordination of assessment and quality assurance. There is also a need for external bodies to provide a consistent policy and funding environment.

Practical implications

The findings illustrate the need for strong partnerships, for programmes that are designed from the ground up as apprenticeships, and for effective integration of apprentices into the organisation's working environment.

Originality/value

This study updates and adds to the literature on DAs and work-integrated higher education. It emphasises three aspects that have hitherto been given little attention: the value of DAs for public-sector recruitment and for creating social mobility within the existing workforce, and the importance of ensuring apprenticeships are aligned with organisational objectives.