bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal whole-sequence-based plasmid typing and its utility to prediction of host range and epidemiological surveillance
Authors: Robertson James , Bessonov Kyrylo , Schonfeld Justin , Nash John H. E.
Published: September 2020

Bacterial plasmids play a large role in allowing bacteria to adapt to changing environments and can pose a significant risk to human health if they confer virulence and antimicrobial resistance (AMR). Plasmids differ significantly in the taxonomic breadth of host bacteria in which they can successfully replicate, this is commonly referred to as ‘host range’ and is usually described in qualitative terms of ‘narrow’ or ‘broad’. Understanding the host range potential of plasmids is of great interest due to their ability to disseminate traits such as AMR through bacterial populations and into human pathogens. We developed the MOB-suite to facilitate characterization of plasmids and introduced a whole-sequence-based classification system based on clustering complete plasmid sequences using Mash distances (https://github.com/phac-nml/mob-suite). We updated the MOB-suite database from 12 091 to 23 671 complete sequences, representing 17 779 unique plasmids. With advances in new algorithms for rapidly calculating average nucleotide identity (ANI), we compared clustering characteristics using two different distance measures – Mash and ANI – and three clustering algorithms on the unique set of plasmids. The plasmid nomenclature is designed to group highly similar plasmids together that are unlikely to have multiple representatives within a single cell. Based on our results, we determined that clusters generated using Mash and complete-linkage clustering at a Mash distance of 0.06 resulted in highly homogeneous clusters while maintaining cluster size. The taxonomic distribution of plasmid biomarker sequences for replication and relaxase typing, in combination with MOB-suite whole-sequence-based clusters have been examined in detail for all high-quality publicly available plasmid sequences. We have incorporated prediction of plasmid replication host range into the MOB-suite based on observed distributions of these sequence features in combination with known plasmid hosts from the literature. Host range is reported as the highest taxonomic rank that covers all of the plasmids which share replicon or relaxase biomarkers or belong to the same MOB-suite cluster code. Reporting host range based on these criteria allows for comparisons of host range between studies and provides information for plasmid surveillance.
Quality evaluation of macaroons added with moringa leaf
(Moringa oleifera Lam.) and green tea
powder
Authors: Baek Chae-Wan , Lee Jeung-Hee
Published: September 2020

The quality characteristics and antioxidant activities of macaroons added with
5% and 7.5% of moringa leaf and green tea powder were evaluated.
Moringa macaroons were more bright and yellow-reddish than green tea macaroons
that showed a strong green color. The spread factor of macaroons decreased
significantly with the increasing powder content. The fracturability and
cohesiveness increased in the macaroons added with powder whereas the hardness
decreased. The total phenolics (TPC) and total flavonoid contents (TFC) of
macaroons with green tea were significantly higher than those of macaroons with
moringa, resulting in higher DPPH radical scavenging capacity and ferric
reducing antioxidant power (p<0.05); these values increased with
increasing moringa leaf or green tea powder content (p<0.05). Antioxidant
activity has a higher correlation with TFC than TPC. The sensory intensities of
greenness, grass flavor, green taste and chewiness were higher in macaroons with
green tea than in macaroon with moringa. The sensory taste, aroma, and texture
properties were better, and the overall acceptability was higher in macaroons
added with green tea than that with moringa. In this study, green tea was found
to be an excellent ingredient for manufacture of macaroons with sensory
preference as functional dessert bakery products with high antioxidant
power.
Identification and characterization of the proteolytic microorganism
isolated from salt mackerel
Authors: Kwon Tae-Hyung , Lee Jong-Hwa
Published: September 2020

Mackerel (Scomber japonicus) is one of the most important
cultured marine species on the southern coast of Korea. However, microbiological
spoilage of mackerel can occur because of bacteria, yeast, and molds. Therefore,
in this study, we investigated the chemical composition of salt mackerel and
characterized and identified proteolytic microorganisms isolated from salt
mackerel. The moisture, crude protein, crude lipid and crude ash contents of
salt mackerel were found to be 62.1%, 17.3%, 16.3%, and
2.6%, respectively. Eleven microorganism strains were isolated from salt
mackerel and characterized to determine the optimum pH and temperature for their
growth and their viability in sodium chloride. Based on determination of 18S
rRNA genes and 16S rRNA genes. the dominant yeast and bacteria species
Rhodotorula glutinis and
Escherichia hermannii, respectively. R. glutinis
and
E. hermannii
showed optimum growth at 25°C, pH 7.0 and 8% and
6% sodium chloride, respectively.
Topological Tuning of DNA Mobility in Entangled Solutions of Supercoiled Plasmids
Authors: Smrek Jan , Garamella Jonathan , Robertson-Anderson Rae , Michieletto Davide
Published: September 2020

Understanding the behaviour of ring polymers in dense solutions is one of the most intriguing problems in polymer physics with far-reaching implications from material science to genome biology. Thanks to its natural occurrence in circular form, DNA has been intensively employed as a proxy to study the fundamental physics of ring polymers in different topological states. Yet, torsionally constrained – such as supercoiled – topologies have been largely neglected so far. Extreme entanglement and high supercoiling levels are commonly found in the genetic material of both pro- and eukaryotes and, at the same time, the applicability of existing theoretical models to dense supercoiled DNA is unknown. To address this gap, here we couple large scale Molecular Dynamics (MD) simulations of twistable chains together with Differential Dynamic Microscopy (DDM) of entangled supercoiled DNA plasmids. We discover that, strikingly, and contrarily to what is generally assumed in the literature, a higher degree of supercoiling increases the average size of plasmids in entangled solutions. At the same time, we discover that this is accompanied by an unexpected enhancement in DNA mobility. We reconcile these apparently contradicting findings as due to the fact that supercoiling drives highly asymmetric plasmid conformations, decreases inter-plasmids entanglements and, in particular, reduces the number of threadings between DNA rings. Our numerical and experimental results also suggest a way to topologically tune DNA mobility via supercoiling, thus enabling the orthogonal control over the (micro)rheology of DNA-based complex fluids with respect to other traditional methods such as DNA length or concentration.
A high-throughput method for measuring critical thermal limits of leaves by chlorophyll imaging fluorescence
Authors: Arnold Pieter A. , Briceño Verónica F. , Gowland Kelli M. , Catling Alexandra A. , Bravo León A. , Nicotra Adrienne B.
Published: September 2020

Plant thermal tolerance is a crucial research area as the climate warms and extreme weather events become more frequent. Leaves exposed to temperature extremes have inhibited photosynthesis and will accumulate damage to photosystem II (PSII) if tolerance thresholds are exceeded. Temperature-dependent changes in basal chlorophyll fluorescence (T-F0) can be used to identify the critical temperature at which PSII is inhibited. We developed and tested a high-throughput method for measuring the critical temperatures for PSII at low (CTMIN) and high (CTMAX) temperatures using a Maxi-Imaging fluorimeter and a thermoelectric Peltier plate heating/cooling system. We examined how experimental conditions: wetvsdry surfaces for leaves and heating/cooling rate, affectCTMINandCTMAXacross four species.CTMAXestimates were not different whether measured on wet or dry surfaces, but leaves were apparently less cold tolerant when on wet surfaces. Heating/cooling rate had a strong effect on bothCTMAXandCTMINthat was species-specific. We discuss potential mechanisms for these results and recommend settings for researchers to use when measuringT-F0. The approach that we demonstrated here allows the high-throughput measurement of a valuable ecophysiological parameter that estimates the critical temperature thresholds of leaf photosynthetic performance in response to thermal extremes.
Performance Assessment of First-Generation Anti-SARS-CoV-2 Serological Assays
Authors: Imam Mehjabeen , Khawaja Shabnum , Naz Arshi , Siddiqui Ahson , Nafees Tehmina S. , Younus Amber , Shamsi Usama , Shabir Imran , Ahmed Shakir , Tariq Naveen , Tariq Salman , Shamsi Tahir S.
Published: September 2020

The clinical and epidemiological use of SARS-CoV-2 antibody assays is under debate with urgent need to validate and verify the performance of SARS-CoV-2 serologic assays. We aim to assess the clinical and analytical performance of three commercial serological assays of SARS-CoV-2, comparing three anti-SARS-CoV-2-IgG ELISA and identifying the seroconversion and seroprevalence in our population.

A cross sectional study conducted from April 2020 to July 2020 at National Institute of Blood disease and Bone Marrow Transplantation Karachi, Pakistan with sample size of 404, enrolled consecutively. Participants were categorized into four groups’ namely convalescent plasmadonors (CPDs n=239), health care professionals (HCPs n=44), healthy blood donors (HBDs n=70) and from community (n=51).

We evaluated the performance of Elecsys anti-SARS-CoV-2 electrochemiluminescence (ECLIA) assay on Cobas-e411 by Roche, three qualitative anti-SARS-CoV-2-IgG enzyme linked imunosorbant assay (ELISA) by (Generic assays, Euroimmun & Omega diagnostics), one quantitative ELISA assay by AESKU Diagnostics and two immune chromatography(ICT) kits namely InstaTest™ by CORTEZ and TEST IT by TURKLAB.

From total 404 subjects, 322 (83.5%) were males. Mean age was 36.79±11.95 years. Among 239 in CPDs group, 202(84.5%) showed positive antibodies by ECLIA. The qualitative anti-SARS-CoV-2 IgG ELISA was positive in 174 (72.8%) and quantitative IgG in 180(75.3%) with mean titer of 56.7 ±39.7 U/ml. Sensitivity and specificity of ECLIA were 97.44& 99%, ELISA by Generic assays were 67.85% and 89.9%; Euroimmun had 90.38% and 94.9%; Omega Diagnostics 96.4% and 95% and the AESKULISA 93.75% and 100% respectively. Seroconversion was found to be 53.8% and 77.77% within 7 -8 days and 12 to 14 days post onset of symptoms respectively. ICT had more specificity but less sensitivity. Seroprevalence was found to be 84.5%, 40.9% and 21.4% in CPDs, HCPs and HBDs respectively.

The Roche ECLIA, qualitative ELISA by Omega Diagnostics & Euroimmun showed higher sensitivity as well as higher specificity. Quantitative ELISA has higher specificity and relatively high sensitivity. Significant numbers of COVID patients do not have detectable antibodies by all assays.
Robust normalization and transformation techniques for constructing gene coexpression networks from RNA-seq data
Authors: Johnson Kayla A , Krishnan Arjun
Published: September 2020

Background

Constructing gene coexpression networks is a powerful approach for analyzing high-throughput gene expression data towards module identification, gene function prediction, and disease-gene prioritization. While optimal workflows for constructing coexpression networks – including good choices for data pre-processing, normalization, and network transformation – have been developed for microarray-based expression data, such well-tested choices do not exist for RNA-seq data. Almost all studies that compare data processing/normalization methods for RNA-seq focus on the end goal of determining differential gene expression.

Results

Here, we present a comprehensive benchmarking and analysis of 30 different workflows, each with a unique set of normalization and network transformation methods, for constructing coexpression networks from RNA-seq datasets. We tested these workflows on both large, homogenous datasets (Genotype-Tissue Expression project) and small, heterogeneous datasets from various labs (submitted to the Sequence Read Archive). We analyzed the workflows in terms of aggregate performance, individual method choices, and the impact of multiple dataset experimental factors. Our results demonstrate that between-sample normalization has the biggest impact, with trimmed mean of M-values or upper quartile normalization producing networks that most accurately recapitulate known tissue-naive and tissue-specific gene functional relationships.

Conclusions

Based on this work, we provide concrete recommendations on robust procedures for building an accurate coexpression network from an RNA-seq dataset. In addition, researchers can examine all the results in great detail athttps://krishnanlab.github.io/norm_for_RNAseq_coexpto make appropriate choices for coexpression analysis based on the experimental factors of their RNA-seq dataset.
Structural biologists, let’s mind our colors
Authors: Saladi Shyam M. , Maggiolo Ailiena O. , Radford Kate , Clemons William M.
Published: September 2020

In structural biology, most figures of macromolecules are aimed at those well-versed in structure, requiring prior familiarity with scales and commonly used color schemes. Yet, as structural biology becomes democratized with the increasing pace of structure determination, the accessibility of structural data is paramount. Here, we identify three keys, and have written accompanying software plugins, for structural biologists to create figures truer to the hard-won data and clearer across different modes of color vision and to non-expert readers.

Use perceptually uniform colormaps

Consider readers with different modes of color vision

Be explicit about scales and color usage
Clinical interpretation of integrative molecular profiles to guide precision cancer medicine
Authors: Reardon Brendan , Moore Nathaniel D , Moore Nicholas , Kofman Eric , Aldubayan Saud , Cheung Alexander , Conway Jake , Elmarakeby Haitham , Imamovic Alma , Kamran Sophia C. , Keenan Tanya , Keliher Daniel , Konieczkowski David J , Liu David , Mouw Kent , Park Jihye , Vokes Natalie , Dietlein Felix , Van Allen Eliezer M
Published: September 2020

Individual tumor molecular profiling is routinely used to detect single gene-variant (“first-order”) genomic alterations that may inform therapeutic actions -- for instance, a tumor with aBRAFp.V600E variant might be considered for RAF/MEK inhibitor therapy. Interactions between such first-order events (e.g., somatic-germline) and global molecular features (e.g. mutational signatures) are increasingly associated with clinical outcomes, but these “second order” alterations are not yet generally accounted for in clinical interpretation algorithms and knowledge bases. Here, we introduce the Molecular Oncology Almanac (MOAlmanac), a clinical interpretation algorithm paired with a novel underlying knowledge base to enable integrative interpretation of genomic and transcriptional cancer data for point-of-care treatment decision-making and translational hypothesis generation. We compared MOAlmanac to first-order interpretation methodology in multiple retrospective patient cohorts and observed that the inclusion of preclinical and inferential evidence as well as second-order molecular features increased the number of nominated clinical hypotheses. MOAlmanac also performed matchmaking between patient molecular profiles and cancer cell lines to further expand individualized clinical actionability. When applied to a prospective precision oncology trial cohort, MOAlmanac nominated a median of two therapies per patient and identified therapeutic strategies administered in 46% of patient profiles. Overall, we present a novel computational method to perform integrative clinical interpretation of individualized molecular profiles. MOAlmanc increases clinical actionability over conventional approaches by considering second-order molecular features and additional evidence sources, and is available as an open-source framework.
Assessing whitefly diversity to infer about begomovirus dynamics in cassava in Brazil
Authors: Xavier César A.D. , Nogueira Angélica M. , Bello Vinícius H. , Watanabe Luís F. M. , Alves-Júnior Miguel , Barbosa Leonardo F. , Beserra-Junior José E.A. , Boari Alessandra J. , Calegario Renata F. , Gorayeb Eduardo S. , Honorato-Júnior Jaime , Koch Gabriel , Lima Gaus S.A. , Lopes Cristian A. , Mello Raquel N. , Pantoja Késsia F. C. , Silva Fabio N. , Ramos-Sobrinho Roberto , Santana Enilton N. , Silva José W.P. , Krause-Sakate Renate , Zerbini F.M.
Published: September 2020

Plant virus ecology is strongly dependent on that of its vector. The necessity of a competent vector for transmission is a primary ecological factor driving the host range expansion of plant arthropod-borne viruses, with vectors playing an essential role in promoting disease emergence. Cassava begomoviruses severely constrain cassava production in Africa. Curiously, begomoviruses have never been reported in cassava in South America, the center of origin for this crop. It has been hypothesized that the absence of a competent begomoviruses vector that efficiently colonizes cassava is the reason why begomoviruses have not emerged in South America. To test this hypothesis, we performed a country-wide whitefly diversity study in cassava in Brazil. Adults and/or nymphs of whiteflies were collected from sixty-six cassava fields across twelve states representing the main agroecological zones of the country. A total of 1,385 individuals were genotyped based on partial mitochondrial cytochrome oxidase I (mtCOI) sequences. A high species richness was observed, with five previously described species and two putative new ones. The most prevalent species wereTetraleurodes acaciaeandBemisia tuberculata, representing over 75% of the analyzed individuals. Although we detected, for the first time, the presence ofBemisia tabaciMiddle East-Asia Minor 1 (BtMEAM1) colonizing cassava in Brazil, it was not prevalent. The species composition varied across regions, with fields in the Northeast region showing a higher diversity. These results expand our knowledge of whitefly diversity in cassava and support the hypothesis that begomovirus epidemics have not occurred in cassava in Brazil due to the absence of competent vector populations. However, they indicate an ongoing adaptation process ofBtMEAM1 to cassava, increasing the likelihood of begomovirus emergence in this crop in the near future.
Establishment of a reverse genetics system for SARS-CoV-2 using circular polymerase extension reaction
Authors: Torii Shiho , Ono Chikako , Suzuki Rigel , Morioka Yuhei , Anzai Itsuki , Fauzyah Yuzy , Maeda Yusuke , Kamitani Wataru , Fukuhara Takasuke , Matsuura Yoshiharu
Published: September 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the causative agent of coronavirus disease 2019 (COVID-19). While the development of specific treatments and a vaccine is urgently needed, functional analyses of SARS-CoV-2 have been limited by the lack of convenient mutagenesis methods. In this study, we established a PCR-based, bacterium-free method to generate SARS-CoV-2 infectious clones. Recombinant SARS-CoV-2 could be rescued at high titer with high accuracy after assembling 10 SARS-CoV-2 cDNA fragments by circular polymerase extension reaction (CPER) and transfection of the resulting circular genome into susceptible cells. Notably, the construction of infectious clones for reporter viruses and mutant viruses could be completed in two simple steps: introduction of reporter genes or mutations into the desirable DNA fragments (~5,000 base pairs) by PCR and assembly of the DNA fragments by CPER. We hope that our reverse genetics system will contribute to the further understanding of SARS-CoV-2.
The Impact of Oxytocin on Neurite Outgrowth and Synaptic Proteins inMagel2-Deficient Mice
Authors: Reichova Alexandra , Schaller Fabienne , Bukatova Stanislava , Bacova Zuzana , Muscatelli Françoise , Bakos Jan
Published: September 2020

Oxytocin contributes to the regulation of cytoskeletal and synaptic proteins and could therefore affect the mechanisms of neurodevelopmental disorders, including autism. Both the Prader-Willi syndrome and Schaaf-Yang syndrome exhibit autistic symptoms involving theMAGEL2gene.Magel2-deficient mice show a deficit in social behavior that is rescued following postnatal administration of oxytocin. Here, inMagel2-deficient mice, we showed that the neurite outgrowth of primary cultures of immature hippocampal neurons is reduced. Treatment with oxytocin, but not retinoic acid, reversed this abnormality. In the hippocampus ofMagel2-deficient pups, we further demonstrated that several transcripts of neurite outgrowth-associated proteins, synaptic vesicle proteins, and cell-adhesion molecules are decreased. In the juvenile stage, when neurons are mature, normalization or even overexpression of most of these markers was observed, suggesting a delay in the neuronal maturation ofMagel2-deficient pups. Moreover, we found reduced transcripts of the excitatory postsynaptic marker,Psd95in the hippocampus and we observed a decrease of PSD95/VGLUT2 colocalization in the hippocampal CA1 and CA3 regions inMagel2-deficient mice, indicating a defect in glutamatergic synapses. Postnatal administration of oxytocin upregulated postsynaptic transcripts in pups; however, it did not restore the level of markers of glutamatergic synapses inMagel2-deficient mice. Overall,Magel2deficiency leads to abnormal neurite outgrowth and reduced glutamatergic synapses during development, suggesting abnormal neuronal maturation. Oxytocin stimulates the expression of numerous genes involved in neurite outgrowth and synapse formation in early development stages. Postnatal oxytocin administration has a strong effect in development that should be considered for certain neuropsychiatric conditions in infancy.
Crystal structure of GH43 exo-β-1,3-galactanase from the basidiomycetePhanerochaete chrysosporiumprovides insights into the mechanism of bypassing side chains
Authors: Matsuyama Kaori , Kishine Naomi , Fujimoto Zui , Sunagawa Naoki , Kotake Toshihisa , Tsumuraya Yoichi , Samejima Masahiro , Igarashi Kiyohiko , Kaneko Satoshi
Published: September 2020

Arabinogalactan proteins (AGPs) are functional plant proteoglycans, but their functions are largely unexplored, mainly because of the complexity of the sugar moieties, which are generally analyzed with the aid of glycoside hydrolases. In this study, we solved the apo and liganded structures of exo-β-1,3-galactanase from the basidiomycetePhanerochaete chrysosporium(Pc1,3Gal43A), which specifically cleaves AGPs. It is composed of a glycoside hydrolase family 43 subfamily 24 (GH43_sub24) catalytic domain together with a carbohydrate-binding module family (CBM) 35 binding domain. GH43_sub24 lacks the catalytic base Asp that is conserved among other GH43 subfamilies. Crystal structure and kinetic analyses indicated that the tautomerized imidic acid function of Gln263 serves instead as the catalytic base residue.Pc1,3Gal43A has three subsites that continue from the bottom of the catalytic pocket to the solvent. Subsite -1 contains a space that can accommodate the C-6 methylol of Gal, enabling the enzyme to bypass the β-1,6-linked galactan side chains of AGPs. Furthermore, the galactan-binding domain in CBM35 has a different ligand interaction mechanism from other sugar-binding CBM35s. Some of the residues involved in ligand recognition differ from those of galactomannan-binding CBM35, including substitution of Trp for Gly, which affects pyranose stacking, and substitution of Asn for Asp in the lower part of the binding pocket.Pc1,3Gal43A WT and its mutants at residues involved in substrate recognition are expected to be useful tools for structural analysis of AGPs. Our findings should also be helpful in engineering designer enzymes for efficient utilization of various types of biomass.
Impacts of sex ratio meiotic drive on genome structure and defense in a stalk-eyed fly
Authors: Reinhardt Josephine A. , Baker Richard H. , Zimin Aleksey V. , Ladias Chloe , Paczolt Kimberly A. , Werren John H. , Hayashi Cheryl Y. , Wilkinson Gerald S.
Published: September 2020

Some stalk-eyed flies in the genus Teleopsis carry selfish genetic elements that induce sex ratio meiotic drive (SR) and impact the fitness of male and female carriers. Here, we produced a chromosome-level genome assembly of the stalk-eyed fly, T. dalmanni, to elucidate patterns of genomic divergence associated with the presence of drive elements. We find evidence for multiple nested inversions along the sex ratio haplotype and widespread differentiation and divergence between XSR and XSR along the entire chromosome. These include a striking XSR-specific expansion of an array of partial copies of JASPer, a gene necessary for maintenance of euchromatin and regulation of transposable element expression (TEs). In addition, the genome contains tens of thousands of TE insertions and hundreds of transcriptionally and insertionally active TE families. Moreover, we find that several TE families are differentially expressed and/or present at a different copy number in SR male testes, suggesting an association between these two categories of selfish genetic elements in this species. We identify T. dalmanni orthologs of genes involved in genome defense via the piRNA pathway, including core members maelstrom, piwi and Argonaute3, that have diverged in sequence, expression or copy number between the SR and standard (ST) X chromosomes, consistent with altered TE regulation in flies carrying a sex ratio X chromosome. Overall, the evidence suggests that this ancient XSR polymorphism has had a variety of impacts on repetitive DNA and its regulation in this species.
A graph neural network model to estimate cell-wise metabolic flux using single cell RNA-seq data
Authors: Alghamdi Norah , Chang Wennan , Dang Pengtao , Lu Xiaoyu , Wan Changlin , Gampala Silpa , Huang Zhi , Wang Jiashi , Ma Qin , Zang Yong , Fishel Melissa , Cao Sha , Zhang Chi
Published: September 2020

The metabolic heterogeneity, and metabolic interplay between cells and their microenvironment have been known as significant contributors to disease treatment resistance. However, with the lack of a mature high-throughput single cell metabolomics technology, we are yet to establish systematic understanding of intra-tissue metabolic heterogeneity and cooperation phenomena among cell populations. To mitigate this knowledge gap, we developed a novel computational method, namely scFEA (single cell Flux Estimation Analysis), to infer single cell fluxome from single cell RNA-sequencing (scRNA-seq) data. scFEA is empowered by a comprehensively reconstructed human metabolic map into a factor graph, a novel probabilistic model to leverage the flux balance constraints on scRNA-seq data, and a novel graph neural network based optimization solver. The intricate information cascade from transcriptome to metabolome was captured using multi-layer neural networks to fully capitulate the non-linear dependency between enzymatic gene expressions and reaction rates. We experimentally validated scFEA by generating an scRNA-seq dataset with matched metabolomics data on cells of perturbed oxygen and genetic conditions. Application of scFEA on this dataset demonstrated the consistency between predicted flux and metabolic imbalance with the observed variation of metabolite abundance in the matched metabolomics data. We also applied scFEA on five publicly available scRNA-seq and spatial transcriptomics datasets and identified context and cell group specific metabolic variations. The cell-wise fluxome predicted by scFEA empowers a series of downstream analysis including identification of metabolic modules or cell groups that share common metabolic variations, sensitivity evaluation of enzymes with regards to their impact on the whole metabolic flux, and inference of cell-tissue and cell-cell metabolic communications.
Mechanism of cell polarisation and first lineage segregation in the human embryo
Authors: Zhu Meng , Shahbazi Marta N. , Martin Angel , Zhang Chuanxin , Sozen Berna , Borsos Mate , Mandelbaum Rachel S. , Paulson Richard J. , Mole Matteo A. , Esbert Marga , Scott Richard T. , Campbell Alison , Fishel Simon , Gradinaru Viviana , Zhao Han , Wu Keliang , Chen Zijiang , Seli Emre , de los Santos Maria J. , Zernicka-Goetz Magdalena
Published: September 2020

The formation of differential cell lineages in the mammalian blastocyst from the totipotent zygote is crucial for implantation and the success of the whole pregnancy. The first lineage segregation generates the polarised trophectoderm (TE) tissue, which forms the placenta, and the apolar inner cell mass (ICM), which mainly gives rise to all foetal tissues and also the yolk sac1–3. The mechanism underlying this cell fate segregation has been extensively studied in the mouse embryo4,5. However, when and how it takes place in the human embryo remains unclear. Here, using time-lapse imaging and 325 surplus human embryos, we provide a detailed characterisation of morphological events and transcription factor expression and localisation to understand how they lead to the first lineage segregation in human embryogenesis. We show that the first lineage segregation of the human embryo is triggered by cell polarisation that occurs at the 8-cell stage in two sequential steps. In the first step, F-actin becomes apically polarised concomitantly with embryo compaction. In the second step, the Par complex becomes polarised to form the apical cellular domain. Mechanistically, we show that activation of Phospholipase C (PLC) triggers actin polarisation and is therefore essential for apical domain formation, as is the case in mouse embryos6. Finally, we show that, in contrast to the mouse embryo, the key extra-embryonic determinant GATA37,8is expressed not only in extra-embryonic lineage precursors upon blastocyst formation. However, the cell polarity machinery enhances the expression and nuclear accumulation of GATA3. In summary, our results demonstrate for the first time that cell polarisation reinforces the first lineage segregation in the human embryo.
Negative short-range genomic autocorrelation of causal effects on human complex traits
Authors: Schoech Armin P. , Weissbrod Omer , O’Connor Luke J. , Patterson Nick , Shi Huwenbo , Reshef Yakir , Price Alkes L.
Published: September 2020

Most models of complex trait genetic architecture assume that signed causal effect sizes of each SNP (defined with respect to the minor allele) are uncorrelated with those of nearby SNPs, but it is currently unknown whether this is the case. We develop a new method, autocorrelation LD regression (ACLR), for estimating the genome-wide autocorrelation of causal minor allele effect sizes as a function of genomic distance. Our method estimates these autocorrelations by regressing the products of summary statistics on distance-dependent LD scores. We determined that ACLR robustly assesses the presence or absence of nonzero autocorrelation, producing unbiased estimates with well-calibrated standard errors in null simulations regardless of genetic architecture; if true autocorrelation is nonzero, ACLR correctly detects its sign, although estimates of the autocorrelation magnitude are susceptible to bias in cases of certain genetic architectures. We applied ACLR to 31 diseases and complex traits from the UK Biobank (average N=331K), meta-analyzing results across traits. We determined that autocorrelations were significantly negative at distances of 1-50bp (P = 8 × 10−6, point estimate −0.35 ±0.08) and 50-100bp (P = 2 × 10−3, point estimate −0.33 ± 0.11). We show that the autocorrelation is primarily driven by pairs of SNPs in positive LD, which is consistent with the expectation that linked SNPs with opposite effects are less impacted by natural selection. Our findings suggest that this mechanism broadly affects complex trait genetic architectures, and we discuss implications for association mapping, heritability estimation, and genetic risk prediction.
Dissociated development of speech and limb sensorimotor learning in stuttering: speech auditory-motor learning is impaired in both children and adults who stutter
Authors: Kim Kwang S. , Daliri Ayoub , Flanagan John Randall , Max Ludo
Published: September 2020

Stuttering is a neurodevelopmental disorder of speech fluency. Various experimental paradigms have demonstrated that affected individuals show limitations in sensorimotor control and learning. However, controversy exists regarding two core aspects of this perspective. First, it has been claimed that sensorimotor learning limitations are detectable only in adults who stutter (after years of coping with the disorder) but not during childhood close to the onset of stuttering. Second, it remains unclear whether stuttering individuals' sensorimotor learning limitations affect only speech movements or also unrelated effector systems involved in nonspeech movements. We report data from separate experiments investigating speech auditory-motor learning (N = 60) and limb visuomotor learning (N = 84) in both children and adults who stutter versus matched nonstuttering individuals. Both children and adults who stutter showed statistically significant limitations in speech auditory-motor adaptation with formant-shifted feedback. This limitation was more profound in children than in adults and in younger children versus older children. Between-group differences in the adaptation of reach movements performed with rotated visual feedback were subtle but statistically significant for adults. In children, even the nonstuttering groups showed limited visuomotor adaptation just like their stuttering peers. We conclude that sensorimotor learning is impaired in individuals who stutter, and that the ability for speech auditory-motor learning -- which was already adult-like in 3-6 year-old typically developing children -- is severely compromised in young children near the onset of stuttering. Thus, motor learning limitations may play an important role in the fundamental mechanisms contributing to the onset of this speech disorder.
Response of coral reef dinoflagellates to nanoplastics under experimental conditions
Authors: Ripken Christina , Khalturin Konstantin , Shoguchi Eiichi
Published: September 2020

Plastic products contribute heavily to anthropogenic pollution of the oceans. Small plastic particles in the micro- and nanoscale ranges have been found in all marine ecosystems, but little is known about their effects upon marine organisms. In this study we examine changes in cell growth, aggregation, and gene expression of two symbiotic dinoflagellates of the family Symbiodiniaceae,Symbiodinium tridacnidorum(clade A3) andCladocopiumsp. (clade C), under exposure to 42-nm polystyrene beads. In laboratory experiments, cell number and aggregation were reduced after 10 days of nanoplastic exposure at 0.01, 0.1, and 10 mg/L concentrations, but no clear correlation with plastic concentration was observed. Genes involved in dynein motor function were upregulated compared to control conditions, while genes related to photosynthesis, mitosis, and intracellular degradation were downregulated. Overall, nanoplastic exposure led to more genes being downregulated than upregulated and the number of genes with altered expression was larger inCladocopiumsp. than inS. tridacnidorum, suggesting different sensitivity to nanoplastic between species. Our data show that nanoplastic inhibits growth and alters aggregation properties of microalgae, which may negatively affect the uptake of these indispensable symbionts by coral reef organisms.
Identification of determinants of differential chromatin accessibility through a massively parallel genome-integrated reporter assay
Authors: Hammelman Jennifer , Krismer Konstantin , Banerjee Budhaditya , Gifford David K. , Sherwood Richard I.
Published: September 2020

A key mechanism in cellular regulation is the ability of the transcriptional machinery to physically access DNA. Transcription factors interact with DNA to alter the accessibility of chromatin, which enables changes to gene expression during development or disease or as a response to environmental stimuli. However, the regulation of DNA accessibility via the recruitment of transcription factors is difficult to study in the context of the native genome because every genomic site is distinct in multiple ways. Here we introduce the multiplexed integrated accessibility assay (MIAA), an assay that measures chromatin accessibility of synthetic oligonucleotide sequence libraries integrated into a controlled genomic context with low native accessibility. We apply MIAA to measure the effects of sequence motifs on cell type–specific accessibility between mouse embryonic stem cells and embryonic stem cell–derived definitive endoderm cells, screening 7905 distinct DNA sequences. MIAA recapitulates differential accessibility patterns of 100-nt sequences derived from natively differential genomic regions, identifying E-box motifs common to epithelial–mesenchymal transition driver transcription factors in stem cell–specific accessible regions that become repressed in endoderm. We show that a single binding motif for a key regulatory transcription factor is sufficient to open chromatin, and classify sets of stem cell–specific, endoderm-specific, and shared accessibility-modifying transcription factor motifs. We also show that overexpression of two definitive endoderm transcription factors, T and Foxa2, results in changes to accessibility in DNA sequences containing their respective DNA-binding motifs and identify preferential motif arrangements that influence accessibility.
Product deletion and supply chain repercussions: risk management using FMEA
Authors: Zhu Qingyun , Golrizgashti Seyedehfatemeh , Sarkis Joseph
Published: September 2020

Purpose

Product portfolio management is a strategic concern. Product portfolio management includes decisions associated with adding new products, maintaining existing products and deleting or phasing out problematic products. This paper first introduces a framework to identify risks of product deletion along supply chain activities. It utilizes failure mode and effects analysis (FMEA) to identify, analyse and evaluate product deletion risks on supply chains and proposes managerial implications for risk management in dynamic business scenarios. It is meant to build upon and address a gap in the product deletion and supply chain linkage literature.

Design/methodology/approach

FMEA is utilized in this study to structure and manage potential risks in product deletion decision-making on supply chains. FMEA is based on an analysis of severity, occurrence and detectability of failure modes. FMEA provides methods to help identify managerial preventive solutions to avoid and mitigate risk consequences of such decisions.

Findings

Ten top product deletion risks are identified in this study; discussions of their negative impact on supply chain performance, and possible managerial recommendations are followed for risk control, monitor and elimination.

Practical implications

Findings help managers to predict, avoid and mitigate risk consequences of product deletion decisions; especially those related to the supply chain. A framework to structure various risks of product deletion in the supply chain can be useful to both practitioners and researchers.

Originality/value

This study advances product portfolio management through enhanced understanding of product deletion decision-making in organizations; and especially contributes to a broader investigation of such decisions in supply chain management. It also structures the factors that play a role in identifying risks.
PMSM speed control based on intelligent sliding mode technique
Authors: Tavoosi Jafar
Published: September 2020

Purpose

The purpose of this paper is to present a novel intelligent backstepping sliding mode control for an experimental permanent magnet synchronous motor.

Design/methodology/approach

A novel recurrent radial basis function network (RBFN) is used to is used to approximate unknown nonlinear functions in permanent magnet synchronous motor (PMSM) dynamics. Then, using the functions obtained from the neural network, it is possible to design a model-based and precise controller for PMSM using the immersive modeling method.

Findings

Experimental results indicate the appropriate performance of the proposed method.

Originality/value

This paper presents a novel intelligent backstepping sliding mode control for an experimental permanent magnet synchronous motor. A novel recurrent RBFN is used to is used to approximate unknown nonlinear functions in PMSM dynamics.
Performance assessment of controller designed for electrical systems with second order dynamics
Authors: Begum K. Ghousiya
Published: September 2020

Purpose

An assessment technique that analyzes the servo and regulatory characteristics of the proportional integral derivative controller is designed for time-delayed second-order stable processes.

Design/methodology/approach

The minimum theoretical error expression for integral of the absolute errors (IAE_o) is obtained from the preferred servo and regulatory transfer functions dependent on the step changes in reference and load variables.

Findings

The error-based index is outlined to estimate the controller that is derived using internal model-based control or direct synthesis method. The ratio between derived IAE_o and the IAE_actual gained from the loop response that experiences step input variations gives rise to a dimensionless error index. This error index measures the behaviour of the controller by considering the index value. If the error index value is larger than 0.8, then the effort taken by the controller is good or else retuning is expected.

Originality/value

The efficacy of the index to validate the controller is verified by applying on a few second-order electrical processes. The results are simulated for both reference tracking and load rejection tasks to demonstrate the rationality of the presented index.
Individual knowledge creation ability: dispositional antecedents and relationship to innovative performance
Authors: Sarwat Nosheen , Abbas Muhammad
Published: September 2020

Purpose

The purpose of this study was to understand the effects of creative self-efficacy and affective personal commitment on individuals' knowledge creation and innovative work behaviors.

Design/methodology/approach

This study used a time-lagged field survey to collect data from a diverse sample across various organizations in Pakistan (N = 249 paired responses). Main and mediating effects were tested using bootstrapping technique.

Findings

The results revealed that affective personal commitment and creative self-efficacy significantly predicted supervisory-rated innovative performance directly and indirectly through knowledge creation ability (KCA).

Originality/value

The study uniquely contributed to the body of knowledge by developing and validating scales for KCA and affective personal commitment. In addition, the study contributed to the body of knowledge by examining the antecedents and outcomes of KCA.
Impact of intangible resources (dominant logic) on SMEs innovation performance, the mediating role of dynamic managerial capabilities: evidence from China
Authors: Khan Kashif Ullah , Atlas Fouzia , Ghani Usman , Akhtar Sadia , Khan Farhan
Published: September 2020

Purpose

The purpose of this paper is to examine the important role of intangible resources under resource based view (RBV) such as dominant logic (information filter and learning/routines) and dynamic managerial capabilities (managerial human capital, HC; social capital, SC and managerial cognition, MC) in small and medium sized enterprises (SMEs) innovation performance in Hefei, Anhui province China.

Design/methodology/approach

An empirical study was conducted while distributing 498 questionnaires among different SMEs in Hefei, of which around 429 responses were received. Structural equation modeling (SEM) was employed to test the proposed hypotheses.

Findings

This research study is an endeavor to fill the missing link in the existing literature, and empirical analysis of this research supports all the hypotheses confirming that dominant logic and dynamic managerial capabilities are valuable intangible resources and positively and significantly influence the SMEs innovation performance. Results also indicate that managerial human capital, social capital and managerial cognition (dynamic managerial capabilities) play a significant mediating role between dominant logic and SMEs innovation performance.

Research limitations/implications

The findings suggest that those SMEs which are lacking tangible resources should build and nurture their top management capabilities and dominant logic and SMEs effectively utilizing these intangible resources can enhance their innovation performance.

Practical implications

The findings suggest that SMEs lacking tangible resources should build and nurture their top management capabilities and dominant logic and SMEs effectively utilizing these intangible resources can enhance their innovation performance.

Originality/value

This paper argues theoretically (under RBV and dynamic capabilities view-DCV) and demonstrates empirically that in an emerging economy, i.e. China characterized by highly volatile, dynamic and uncertain competitive environments, SMEs lack tangible resources; therefore, intangible resources (e.g. dominant logic-DL and dynamic managerial capabilities-DMC) are vital for SMEs innovation performance and competitive advantage.
Entrepreneurial characteristics amongst university students: insights for understanding entrepreneurial intentions amongst youths in a developing economy
Authors: Ibidunni Ayodotun Stephen , Mozie Dumebi , Ayeni Adebanji Wlliam A.A.
Published: September 2020

Purpose

This study focussed on investigating the impact of entrepreneurial characteristics on the entrepreneurial intention of university students in Nigeria.

Design/methodology/approach

This research adopted a survey research design via a well-constructed questionnaire. The study's sample size consisted of 354 aspiring student entrepreneurs.

Findings

The result from the statistical analysis revealed that the entrepreneurial characteristics, especially risk tolerance, the need for achievement and the locus of control (LoC) significantly influence students' entrepreneurial intentions.

Research limitations/implications

One implication of this study is that risk tolerance has a positive influence on the ability to identify business opportunities. Thus, when persons pay adequate attention to tolerating risks, they have more chances of identifying business opportunities. Despite the valuable contribution made by this research, an important area of future research is to carry out investigations that use a more robust sample size and a multivariate analysis to identify the impact of entrepreneurial competencies on entrepreneurial intentions of university youths from a cross-country perspective amongst developing economies.

Originality/value

There are very little understanding and empirical evidence about how the entrepreneurial characteristics of the youths, especially those in the formal university system of developing countries like Nigeria, can determine and direct their intentions to venture into entrepreneurship endeavours. This study, therefore, undertakes an interventionist role to investigate the relationship between entrepreneurial characteristics and entrepreneurial intentions of university students in Nigeria.