bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of native and mirror protein structures based on Ramachandran plot analysis by interpretable machine learning models
Authors: Abel Julia , Kaden Marika , Bohnsack Katrin Sophie , Weber Mirko , Leberecht Christoph , Villmann Thomas
Published: September 2020

In this contribution the discrimination between native and mirror models of proteins according to their chirality is tackled based on the structural protein information. This information is contained in the Ramachandran plots of the protein models. We provide an approach to classify those plots by means of an interpretable machine learning classifier - the Generalized Matrix Learning Vector Quantizer. Applying this tool, we are able to distinguish with high accuracy between mirror and native structures just evaluating the Ramachandran plots. The classifier model provides additional information regarding the importance of regions, e.g.α-helices andβ-strands, to discriminate the structures precisely. This importance weighting differs for several considered protein classes.
Fast and inexpensive whole genome sequencing library preparation from intact yeast cells
Authors: Vonesch Sibylle C , Li Shengdi , Tu Chelsea Szu , Hennig Bianca P , Dobrev Nikolay , Steinmetz Lars M
Published: September 2020

Through the increase in the capacity of sequencing machines massively parallel sequencing of thousands of samples in a single run is now possible. With the improved throughput and resulting drop in the price of sequencing, the cost and time for preparation of sequencing libraries have become the major bottleneck in large-scale experiments. Methods using a hyperactive variant of the Tn5 transposase efficiently generate libraries starting from cDNA or genomic DNA in a few hours and are highly scalable. For genome sequencing, however, the time and effort spent on genomic DNA isolation limits the practicability of sequencing large numbers of samples. Here, we describe a highly scalable method for preparing high quality whole-genome sequencing libraries directly from yeast cultures in less than three hours at 34 cents per sample. We skip the rate-limiting step of genomic DNA extraction by directly tagmenting yeast spheroplasts and add a nucleosome release step prior to enrichment PCR to improve the evenness of genomic coverage. Resulting libraries do not show any GC-bias and are comparable in quality to libraries processed from genomic DNA with a commercially available Tn5-based kit. We use our protocol to investigate CRISPR/Cas9 on- and off-target edits and reliably detect edited variants and shared polymorphisms between strains. Our protocol enables rapid preparation of unbiased and high-quality, sequencing-ready indexed libraries for hundreds of yeast strains in a single day at a low price. By adjusting individual steps of our workflow we expect that our protocol can be adapted to other organisms.
TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin stability
Authors: Balestra Fernando R. , Wolf Benita , Domínguez-Calvo Andrés , Buff Alizée , Averink Tessa , Lipsanen-Nyman Marita , Busso Coralie , Huertas Pablo , Ríos Rosa M. , Gönczy Pierre
Published: September 2020

TRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease characterized by impaired growth and increased tumorigenesis, whose cellular etiology is poorly understood. TRIM37 depletion from tissue culture cells results in supernumerary foci bearing the centriolar protein Centrin. Here, we characterized these centriolar protein assemblies (Cenpas) to uncover the mechanism of action of TRIM37. We established that an atypicalde novoassembly pathway is notably involved in forming Cenpas, which can nevertheless trigger further centriole assembly and act as MTOCs. We found also that Cenpas are present and act similarly in Mulibrey patient cells. Through correlative light electron microscopy, we uncovered that Cenpas correspond to centriole related structures and elongated electron-dense structures with stripes. Importantly, we established that TRIM37 regulates the stability and solubility of the centriolar protein Centrobin. Our findings suggest that elongated Centrobin assemblies are a major constituent of the striped electron dense structures. Furthermore, we established that Cenpas formation upon TRIM37 depletion requires PLK4 activity, as well as two parallel pathways relying respectively on Centrobin and PLK1. Overall, our work uncovers how TRIM37 prevents the formation of Cenpas that would otherwise threaten genome integrity, including possibly in Mulibrey patients.
Azetidines kill Mycobacterium tuberculosis without detectable resistance by blocking mycolate assembly
Authors: Lanne Alice , Cui Yixin , Browne Edward , Craven Philip G. E. , Cundy Nicholas J. , Coltman Nicholas J. , Dale Katie , Feula Antonio , Frampton Jon , Goff Aaron , Hama Salih Mariwan A. , Lang Xingfen , Li Xingjian , Moon Christopher W. , Morton Michael , Pascoe Jordan , Peng Xudan , Portman Vanessa , Press Cara , Schulz-Utermoehl Timothy , Tortorella Micky , Tu Zhengchao , Underwood Zoe E. , Wang Changwei , Yoshizawa Akina , Zhang Tianyu , Waddell Simon J , Bacon Joanna , Neagoie Cleopatra , Fossey John S. , Alderwick. Luke J.
Published: September 2020

Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10 million new cases and 1.5 million deaths in 2019. This global emergency is exacerbated by the emergence of multi-drug-resistant MDR-TB and extensively-drug-resistant XDR-TB, therefore new drugs and new drug targets are urgently required. From a whole-cell phenotypic screen a series of azetidines derivatives termed BGAz, that elicit potent bactericidal activity with MIC99 values <10 μM against drug-sensitive Mycobacterium tuberculosis and MDR-TB were identified. These compounds demonstrate no detectable drug resistance. Mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from existing mycobacterial cell-wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as anti-tubercular chemotherapies.
A single nuclei transcriptomic analysis of the Atlantic salmon gill through smoltification and seawater transfer
Authors: West Alexander C. , Mizoro Yasutaka , Wood Shona H. , Ince Louise M. , Iversen Marianne , Jørgensen Even H. , Nome Torfinn , Sandve Simen Rød , Loudon Andrew S. I. , Hazlerigg David G.
Published: September 2020

Anadromous salmonids begin life adapted to the freshwater environments of their natal streams before a developmental transition, known as smoltification, transforms them into marine-adapted fish. In the wild, the extending photoperiods of spring stimulates smoltification, typified by radical reprogramming of the gill from an ion-absorbing organ to ion-excreting organ. Prior work has highlighted the role of specialized “mitochondrion-rich” cells in delivering this phenotype. However, transcriptomic studies identify thousands of smoltification-driven differentially regulated genes, indicating that smoltification causes a multifaceted, multicellular change; but direct evidence of this is lacking.

Here, we use single-nuclei RNAseq to characterize the Atlantic salmon gill during smoltification and seawater transfer. We identify 20 distinct clusters of nuclei, including known, but also novel gill cell types. These data allow us to isolate cluster-specific, smoltification-induced changes in gene expression. We also show how cellular make-up of the gill changes through smoltification. As expected, we noted an increase in the proportion of seawater mitochondrion-rich cells, however, we also identify a reduction of several immune-related cells. Overall, our results provide unrivaled detail of the cellular complexity in the gill and suggest that smoltification triggers unexpected immune reprogramming directly preceding seawater entry.
Meningeal inflammation in multiple sclerosis induces phenotypic changes in cortical microglia that differentially associate with neurodegeneration
Authors: van Olst Lynn , Rodriguez-Mogeda Carla , Picon-Munoz Carmen , Kiljan Svenja , James Rachel E. , Kamermans Alwin , van der Pol Susanne M.A. , Knoop Lydian , Drost Evelien , Franssen Marc , Schenk Geert , Geurts Jeroen J.G. , Amor Sandra , Mazarakis Nicholas D. , van Horssen Jack , de Vries Helga E. , Reynolds Richard , Witte Maarten E.
Published: September 2020

Meningeal inflammation strongly associates with demyelination and neuronal loss in the underlying cortex of progressive MS patients, contributing to clinical disability. However, the pathological mechanisms of meningeal inflammation-induced cortical pathology are still largely elusive. Using extensive analysis of human post-mortem tissue, we identified two distinct microglial phenotypes, termed MS1 and MS2, in the cortex of progressive MS patients. These phenotypes differed in morphology and protein expression, but both associated with inflammation of the overlying meninges. We could replicate the MS-specific microglial phenotypes in a novelin vivorat model for progressive MS-like meningeal inflammation, with microglia present at 1 month post-induction resembling MS1 microglia whereas those at 2 months acquired an MS2-like phenotype. Interestingly, MS1 microglia were involved in presynaptic displacement and phagocytosis and associated with a relative sparing of neurons in the MS and animal cortex. In contrast, the presence of MS2 microglia coincided with substantial neuronal loss. Taken together, we uncovered that in response to meningeal inflammation, microglia acquire two distinct phenotypes that differentially associate with neurodegeneration in the progressive MS cortex. Our data suggests that these phenotypes occur sequentially and that microglia may lose their protective properties over time, contributing to neuronal loss.
Pathogenic Mutations in the Kinesin-3 Motor KIF1A Diminish Force Generation and Movement Through Allosteric Mechanisms
Authors: Budaitis Breane G. , Jariwala Shashank , Rao Lu , Sept David , Verhey Kristen J. , Gennerich Arne
Published: September 2020

The kinesin-3 motor KIF1A functions in neurons where its fast and superprocessive motility is thought to be critical for long-distance transport. However, little is known about the force-generating properties of kinesin-3 motors. Using optical tweezers, we demonstrate that KIF1A and itsC. eleganshomolog UNC-104 undergo force-dependent detachments at ~3 pN and then rapidly reattach to the microtubule to resume motion, resulting in a sawtooth pattern of clustered force generation events that is unique among the kinesin superfamily. Whereas UNC-104 motors stall before detaching, KIF1A motors do not. To examine the mechanism of KIF1A force generation, we introduced mutations linked to human neurodevelopmental disorders, V8M and Y89D, based on their location in structural elements required for force generation in kinesin-1. Molecular dynamics simulations predict that the V8M and Y89D mutations impair docking of the N-terminal (β9) or C-terminal (β10) portions of the neck linker, respectively, to the KIF1A motor domain. Indeed, both mutations dramatically impair force generation of KIF1A but not the motor’s ability to rapidly reattach to the microtubule track. Homodimeric and heterodimeric mutant motors also display decreased velocities, run lengths, and landing rates and homodimeric Y89D motors exhibit a higher frequency of non-productive, diffusive events along the microtubule. In cells, cargo transport by the mutant motors is delayed. Our work demonstrates the importance of the neck linker in the force generation of kinesin-3 motors and advances our understanding of how mutations in the kinesin motor domain can manifest in disease.
The microbiome affects liver sphingolipids and plasma fatty acids in a murine model of the Western diet based on soybean oil
Authors: Di Rienzi Sara C. , Johnson Elizabeth L. , Waters Jillian L. , Kennedy Elizabeth A. , Jacobson Juliet , Lawrence Peter , Wang Dong Hao , Worgall Tilla S. , Brenna J. Thomas , Ley Ruth E.
Published: September 2020

Studies in mice using germfree animals as controls for microbial colonization have shown that the gut microbiome mediates diet-induced obesity. Such studies use diets rich in saturated fat, however, Western diets in the USA are enriched in soybean oil, composed of unsaturated fatty acids (FAs), either linoleic or oleic acid. Here we addressed whether the microbiome is a variable in fat metabolism in mice on a soybean oil diet. We used conventionally-raised, low-germ, and germfree mice fed for 10 weeks diets either high (HF) or low (LF) in high-linoleic-acid soybean oil as the sole source of fat. All mice, including germfree, gained relative fat weight and consumed more calories on the HF versus LF soybean oil diet. Plasma fatty acid levels were generally dependent on diet, with microbial colonization status affectingiso-C18:0, C20:3n-6, C14:0, and C15:0 levels. Colonization status, but not diet, impacted levels of liver sphingolipids including ceramides, sphingomyelins, and sphinganine. Our results confirm that absorbed fatty acids are mainly a reflection of the diet, and show that microbial colonization influences liver sphingolipid pools.
Genome sequence of the oyster mushroomPleurotus ostreatusstrain PC9
Authors: Lee Yi-Yun , de Ulzurrun Guillermo Vidal-Diez , Schwarz Erich M. , Stajich Jason E. , Hsueh Yen-Ping
Published: September 2020

The oyster mushroomPleurotus ostreatusis a basidiomycete commonly found in the rotten wood and it is one of the most cultivated edible mushrooms globally.P. ostreatusis also a carnivorous fungus, which can paralyze and kill nematodes within minutes. However, the molecular mechanisms of the predator-prey interactions betweenP. ostreatusand nematodes remain unclear. PC9 and PC15 are two model strains ofP. ostreatusand the genomes of both strains have been sequenced and deposited at the Joint Genome Institute (JGI). These two monokaryotic strains exhibit dramatic differences in growth, but because PC9 grows more robustly in laboratory conditions, it has become the strain of choice for many studies. Despite the fact that PC9 is the common strain for investigation, its genome is fragmentary and incomplete relative to that of PC15. To overcome this problem, we used PacBio long reads and Illumina sequencing to assemble and polish a more integrated genome for PC9. Our PC9 genome assembly, distributed across 17 scaffolds, is highly contiguous and includes six telomere-to-telomere scaffolds, dramatically improving the genome quality. We believe that our PC9 genome resource will be useful to the fungal research community investigating various aspects ofP. ostreatusbiology.
Time scales of mixing in an imperforate scleractinian coelenteron
Authors: Williams Sara D. , Patterson Mark R.
Published: September 2020

Coelentera are the largest components by volume in the gastrovascular system connecting polyps in a scleractinian colony. Thus to understand colony connectivity which is predicted to affect corals’ response to environmental change, we must first describe the dynamics inside these gastric cavities of individual polyps. We determined key time scales of mixing in coelentera by using microelectrodes to measure oxygen concentration after a light-to-dark transition in three polyps each of three colonies ofMontastraea cavernosain the laboratory. The gastrovascular system was modeled as an electrical network where voltage represents oxygen concentration, current represents oxygen flux, capacitors represent volume compartments, and resistors represent impedance to oxygen flux. The time constant of mixing, defined as the time needed for the system to disperse 63.2% of the fluid in the coelenteron, was determined from the oxygen dynamics in the coelenteron as modeled by a resistor-capacitor network. Time constants were on the order of three minutes and oxygen dynamics were well fit by the model prediction. However, as polyps depleted oxygen, we observed small magnitude (~ 0.1 ppm), high-frequency fluctuations in oxygen concentration. A power spectral density analysis identified two time scales of high-frequency mixing in the coelenteron. The greatest variance occurred at a period of 48.3 ± 2.8 seconds, with a secondary peak seen at 35.9 ± 2.3 seconds. The microenvironment within polyps ofM. cavernosacan respond as fast or faster than their external environment can fluctuate, thus scleractinian polyps have the capacity to mediate their response to changing environmental conditions.
Effects of age and hearing loss on perceptual and physiological measures of temporal envelope processing and spatial release from speech-on-speech masking
Authors: Patro Chhayakanta , Kreft Heather A. , Wojtczak Magdalena
Published: September 2020

Older adults often experience difficulties understanding speech in adverse listening conditions. These difficulties are partially attributed to auditory temporal-processing deficits associated with aging even in the absence of hearing loss. The aim of this study was to assess effects of age and hearing loss on temporal envelope processing and speech-on-speech masking. Listeners with normal and near-normal hearing across a wide age range (20 to 66 years) were tested using a series of psychophysical (amplitude-modulation detection, gap detection, and interaural-envelope-phase discrimination), physiological (electroencephalographic envelope-following responses), speech perception (spatial release from masking), and cognitive (processing speed) measures. Results showed that: (i) psychophysical measures of monaural and binaural envelope processing and neural measures of envelope processing are not affected by aging after accounting for audiometric hearing loss, (ii) behavioral gap-detection thresholds decline with age, (iii) aging results in a reduction of spatial release from masking, even as speech intensity is amplified in the region of hearing loss, (iv) aging is associated with poorer measures of cognitive function. Although age significantly contributed to a decline in spatial release from speech-on-speech masking, individual differences in envelope processing and in scores from nonauditory cognitive tests used in this study were not significant predictors of speech performance.

Highlights

Age per se does not affect psychophysical and physiological measures of monaural amplitude-modulation processing.

Age does not affect the ability to detect interaural disparities in envelope timing between the ears.

Gap detection thresholds degrades with age even after hearing thresholds are statistically accounted for.

Age, independent of hearing thresholds, can substantially reduce spatial release from masking.

Cognitive ability declines with age. However, such declines do not necessarily cause deficits in spatial release from masking.
Phylo-geo-network and haplogroup analysis of 611 novel Coronavirus (nCov-2019) genomes from India
Authors: Laskar Rezwanuzzaman , Ali Safdar
Published: September 2020

The novel Coronavirus from Wuhan China discovered in December 2019 (nCOV-2019) has since developed into a global epidemic with major concerns about the possibility of the virus evolving into something even more sinister. In the present study we constructed the phylo-geo-network of nCOV-2019 genomes from across India to understand the viral evolution in the country. A total of 611 full length genomes were extracted from different states of India from the EpiCov repository of GISAID initiative and NCBI. Their alignment uncovered 270 parsimony informative sites. Further, 339 genomes were divided into 51 haplogroups. The network revealed the core haplogroup as that of reference sequence NC_045512.2 (Haplogroup A1) with 157 identical sequences present across 16 states. The rest were having not more than ten identical sequences across not more than three locations. Interestingly, some locations with fewer samples have more haplogroups and most haplogroups (41) are localized exclusively to any one state only, suggesting the local evolution of viruses. The two most common lineages are B6 and B1 (Pangolin) whereas clade A2a (Covidex) appears to be the most predominant in India. However, since the pandemic is still emerging, the final outcome will be clear later only.
Is there a role for the RNA-binding protein LARP1 in β-cells?
Authors: Werneck-de-Castro Joao Pedro , Peçanha Flavia Leticia Martins , Silvestre Diego , Bernal-Mizrachi Ernesto
Published: September 2020

Mechanistic target of rapamycin complex 1 (mTORC1) is a cellular rheostat linking nutrient availability and growth factor to cellular protein translation. In pancreatic insulin secreting β-cells, mTORC1 deficiency or chronic hyperactivation leads to diabetes. mTORC1 complexes with La-related protein 1 (LARP1) to specifically regulate the expression of 5’ terminal oligopyrimidine tract (5’TOP) mRNAs which encode proteins of the translation machinery and ribosome biogenesis. We aimed to investigate the role played by LARP1 in β-cellsin vivo. Here we show that LARP1 is the most expressed LARP in mouse islets and human β-cells, being 2-4-fold more abundant than LARP1B, a member of the family that also interacts with mTORC1. Interestingly, β-cells from diabetic patients have higher LARP1 and LARP1B expression suggesting greater protein translation. These studies led us to generate a conditional LARP1 knockout mouse in β-cells (β-Larp1KOmice). These mice exhibit normal levels of all LARP family members includingLarp1B, Larp4, Larp6andLarp7. We did not observe any difference between control andβ-Larp1KOmale mice in body weight gain, glucose levels and glucose tolerance at 8, 14 and 44 weeks of age. Femaleβ-Larp1KOmice also performed normally during the glucose tolerance test. We then challenged theβ-Larp1KOmice with high fat (HFD) or high branched-chain amino acid (BCAA) diets. During the course of 8 weeks in HFD,β-Larp1KOand control mice had similar weight gain and did not show alterations in glucose homeostasis compared to control littermates. BCAA did not impair glucose metabolism up to 8 weeks of diet challenge. However, glucose tolerance was slightly impaired in theβ-Larp1KOmice at 16 weeks under BCAA diet. In conclusion, LARP1 is the most abundant LARP in mouse islets and human β-cells and it is upregulated in diabetic subjects. While the lack of LARP1 specifically in β-cells did not alter glucose homeostasis in basal conditions, long-term high branched-chain amino acid feeding could impair glucose tolerance.
Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation
Authors: Hou Xiaowei , Outhwaite Ian R. , Pedi Leanne , Long Stephen Barstow
Published: September 2020

The calcium release-activated calcium channel Orai regulates Ca2+entry into non-excitable cells and is required for proper immune function. The channel typically opens following the release of Ca2+from the endoplasmic reticulum. Certain pathologic mutations render the channel constitutively open. Here, using one such mutation (H206A), we present a cryo-EM structure of Orai fromDrosophila melanogasterin an open conformation at 3.3 Å resolution. Comparison with previous closed structures reveals that opening occurs through the outward movements of M1 helices that dilate the central pore. Repositionings of a ring of phenylalanine residues (F171) expose previously shielded glycine residues (G170) to the channel pore, despite the absence of significant rotational movement of the associated pore-lining helices. This phenylalanine ring and two rings of flanking hydrophobic amino acids act as a hydrophobic gate to control ion permeation. Extracellular M1-M2 turrets, not evident from previous Orai structures, form an electronegative pore entrance.

Single sentence summary

A structure of the Ca2+channel Orai in an open conformation provides insight into the opening mechanism of the channel and its role in regulating selective Ca2+entry into immune and other non-excitable cells.
MecCog: A knowledge representation framework for genetic disease mechanism
Authors: Kundu Kunal , Darden Lindley , Moult John
Published: September 2020

Motivation

Experimental findings on genetic disease mechanisms are scattered throughout the literature and represented in many ways, including unstructured text, cartoons, pathway diagrams, and network graphs. Integration and structuring of such mechanistic information will greatly enhance its utility.

Results

MecCog is a graphical framework for building integrated representations (mechanism schemas) of mechanisms by which a genetic variant causes a disease phenotype. A MecCog mechanism schema displays the propagation of system perturbations across stages of biological organization, using graphical notations to symbolize perturbed entities and activities, hyperlinked evidence tagging, a mechanism ontology, and depiction of knowledge gaps, ambiguities, and uncertainties. The web platform enables a user to construct, store, publish, browse, query, and comment on schemas. MecCog facilitates the identification of potential biomarkers, therapeutic intervention sites, and critical future experiments.

Availability and Implementation

The MecCog framework is freely available athttp://www.meccog.org.

Contact

jmoult@umd.edu

Supplementary information

Supplementary material is available atBioinformaticsonline.
Comparative genomics ofClostridiumspecies associated with vacuum-packed meat spoilage
Authors: Palevich Nikola , Palevich Faith P. , Maclean Paul H. , Altermann Eric , Gardner Amanda , Burgess Sara , Mills John , Brightwell Gale
Published: September 2020

Bacterial species belonging to theClostridiumgenera have been recognized as causative agents of blown pack spoilage (BPS) in vacuum packed meat products. Whole-genome sequencing of six New Zealand psychrotolerantClostridiumisolates derived from three meat production animal types and their environments was performed to examine their roles in BPS. Comparative genome analyses have provided insight into the genomic diversity and physiology of these bacteria and dividesClostridiainto two separate species clusters. BPS-associatedClostridiaencode a large and diverse spectrum of degradative carbohydrate-active enzymes (CAZymes). In total, 516 glycoside hydrolases (GHs), 93 carbohydrate esterases (CEs), 21 polysaccharide lyases (PLs), 434 glycosyl transferases (GTs) and 211 carbohydrate-binding protein modules (CBM) with predicted activities involved in the breakdown and transport of carbohydrates were identified.Clostridiagenomes have different patterns of CAZyme families and vary greatly in the number of genes within each CAZy category, suggesting some level of functional redundancy. These results suggest that BPS-associatedClostridiaoccupy similar environmental niches but apply different carbohydrate metabolism strategies to be able to co-exist and cause meat spoilage.
Modeling multiple phenotypes in wheat using data-driven genomic exploratory factor analysis and Bayesian network learning
Authors: Momen Mehdi , Bhatta Madhav , Hussain Waseem , Yu Haipeng , Morota Gota
Published: September 2020

Inferring trait networks from a large volume of genetically correlated diverse phenotypes such as yield, architecture, and disease resistance can provide information on the manner in which complex phenotypes are interrelated. However, studies on statistical methods tailored to multi-dimensional phenotypes are limited, whereas numerous methods are available for evaluating the massive number of genetic markers. Factor analysis operates at the level of latent variables predicted to generate observed responses. The objectives of this study were to illustrate the manner in which data-driven exploratory factor analysis can map observed phenotypes into a smaller number of latent variables and infer a genomic latent factor network using 45 agro-morphological, disease, and grain mineral phenotypes measured in synthetic hexaploid wheat lines (Triticum Aestivum L.). In total, eight latent factors including grain yield, architecture, flag leaf-related traits, grain minerals, yellow rust, two types of stem rust, and leaf rust were identified as common sources of the observed phenotypes. The genetic component of the factor scores for each latent variable was fed into a Bayesian network to obtain a trait structure reflecting the genetic interdependency among traits. Three directed paths were consistently identified by two Bayesian network algorithms. Flag leaf-related traits influenced leaf rust, and yellow rust and stem rust influenced grain yield. Additional paths that were identified included flag leaf-related traits to minerals and minerals to architecture. This study shows that data-driven exploratory factor analysis can reveal smaller dimensional common latent phenotypes that are likely to give rise to numerous observed field phenotypes without relying on prior biological knowledge. The inferred genomic latent factor structure from the Bayesian network provides insights for plant breeding to simultaneously improve multiple traits, as an intervention on one trait will affect the values of focal phenotypes in an interrelated complex trait system.
Drosophila melanogasteras a model host to study arbovirus–vector interaction
Authors: Paingankar Mandar S. , Gokhale Mangesh D. , Deobagkar Deepti D. , Deobagkar Dileep N.
Published: September 2020

Arboviruses cause the most devastating diseases in humans and animals worldwide. Several hundred arbovirus are transmitted by mosquitoes, sand flies or ticks and are responsible for more than million deaths annually. Development of a model system is essential to extrapolate the molecular events occurring during infection in the human and mosquito host. Virus overlay protein binding assay (VOPBA) combined with MALDI TOF/TOF MS revealed that Dengue-2 virus (DENV-2) exploits similar protein molecules inDrosophila melanogasterandAedes aegyptifor its infection. Furthermore, the virus susceptibility studies revealed that DENV-2 could propagate inD. melanogaster, and DENV-2 produced in fruit fly is equally infectious toD. melanogasterandAe. aegypti. Additionally, real time PCR analysis revealed that RNAi coupled with JAK-STAT and Toll pathway constitutes an effector mechanism to control the DENV-2 infection in flies. These observations point out thatD. melanogasterharbors all necessary machineries to support the growth of arboviruses. With the availability of well-established techniques for genetic and developmental manipulations,D. melanogaster, offers itself as the potential model system for the study of arbovirus-vector interactions.
All-Trans Retinoic Acid induces synaptic plasticity in human cortical neurons
Authors: Lenz Maximilian , Kruse Pia , Eichler Amelie , Muellerleile Julia , Straehle Jakob , Jedlicka Peter , Beck Jürgen , Deller Thomas , Vlachos Andreas
Published: September 2020

A defining feature of the brain is its ability to adapt structural and functional properties of synaptic contacts in an experience-dependent manner. In the human cortex direct experimental evidence for synaptic plasticity is currently missing. Here, we probed plasticity in human cortical slices using the vitamin A derivative all-trans retinoic acid, which has been suggested as medication for the treatment of neuropsychiatric disorders, e.g., Alzheimer’s disease. Our experiments demonstrate coordinated structural and functional changes of excitatory synapses of superficial (layer 2/3) pyramidal neurons in the presence of all-trans retinoic acid. This synaptic adaptation is accompanied by ultrastructural remodeling of the calcium-storing spine apparatus organelle and requires mRNA-translation. We conclude that all-trans retinoic acid is a potent mediator of synaptic plasticity in the adult human cortex.
Faster model updating in autism during early sensory processing
Authors: Goris Judith , Braem Senne , Van Herck Shauni , Deschrijver Eliane , Wiersema Jan R. , Paton Bryan , Brass Marcel , Todd Juanita
Published: September 2020

Background

Recent theories of autism propose that a core deficit in autism would be a less context-sensitive weighting of prediction errors. There is also first support for this hypothesis on an early sensory level. However, an open question is whether this decreased context-sensitivity is caused by faster updating of one’s model of the world (i.e. higher weighting of new information), proposed by predictive coding theories, or slower model updating. Here, we differentiated between these two hypotheses by investigating how first impressions shape the mismatch negativity (MMN), reflecting early sensory prediction error processing.

Methods

An autism and matched control group (bothn=27) were compared on the multi-timescale MMN paradigm, in which tones were presented that were either standard (frequently occurring) or deviant (rare), and these roles reversed every block. A well-replicated observation is that the initial model (i.e. the standard and deviant sound in the first block) influences MMN amplitudes in later blocks. If autism is characterized by faster model updating, we hypothesized that their MMN amplitudes would be less influenced by the initial context.

Results

We found that MMN responses in the autism group did not differ between the initial deviant and initial standard sounds as they did in the control group.

Conclusions

These results show that individuals with autism are less influenced by initial contexts, confirming that autism is characterized by faster updating of sensory models, as proposed by predictive coding accounts of autism.
Background-suppressed live visualization of genomic loci with an improved CRISPR system based on a split fluorophore
Authors: Chaudhary Narendra , Nho Si-Hyeong , Cho Hayoon , Gantumur Narangerel , Ra Jae Sun , Myung Kyungjae , Kim Hajin
Published: September 2020

The higher-order structural organization and dynamics of the chromosomes play a central role in gene regulation. To explore this structure–function relationship, it is necessary to directly visualize genomic elements in living cells. Genome imaging based on the CRISPR system is a powerful approach but has limited applicability due to background signals and nonspecific aggregation of fluorophores within nuclei. To address this issue, we developed a novel visualization scheme combining tripartite fluorescent proteins with the SunTag system and demonstrated that it strongly suppressed background fluorescence and amplified locus-specific signals, allowing long-term tracking of genomic loci. We integrated the multicomponent CRISPR system into stable cell lines to allow quantitative and reliable analysis of dynamic behaviors of genomic loci. Due to the greatly elevated signal-to-background ratio, target loci with only small numbers of sequence repeats could be successfully tracked, even under a conventional fluorescence microscope. This feature enables the application of CRISPR-based imaging to loci throughout the genome and opens up new possibilities for the study of nuclear processes in living cells.
Crystal structure of 1,1′-{(1E,1′E)-[4,4′-(9H-fluorene-9,9-diyl)bis(4,1-phenylene)]bis(azanylylidene)bis(methanylylidene)}bis(naphthalen-2-ol) dichlorobenzene monosolvate
Authors: Wodajo Ayalew , Tskhovrebov Alexander G. , Le Tuan Anh , Kubasov Alexey S. , Grishina Maria M. , Krutius Oleg N. , Khrustalev Victor N.
Published: September 2020

The bis(anil) molecule of the title compound, C47H32N2O2·C6H4Cl2, contains two anil fragments in the enol–enol form, exhibiting intramolecular O—H...N hydrogen bonds. The two hydroxynaphthalene ring systems are approximately parallel to each other with a dihedral angle of 4.67 (8)° between them, and each ring system makes a large dihedral angle [55.11 (11) and 48.50 (10)°] with the adjacent benzene ring. In the crystal, the bis(anil) molecules form an inversion dimer by a pair of weak C—H...O interactions. The dimers arrange in a one-dimensional column along the b axis via another C—H...O interaction and a π–π stacking interaction between the hydroxynaphthalene ring system with a centroid–centroid distance of 3.6562 (16) Å. The solvent 1,2-dichlorobenzene molecules are located between the dimers and bind neighbouring columns by weak C—H...Cl interactions. Theoretical prediction of potential biological activities was performed, which suggested that the title anil compound can exhibit histone deacetylase SIRT2, histone deacetylase class III and histone deacetylase SIRT1 activities, and will act as inhibitor to aspulvinone dimethylallyltransferase, dehydro-L-gulonate decarboxylase and glutathione thiolesterase.
Corrosion behavior of WB36CN1 steel at different flow rates
Authors: Song Jian , Gao Zhiming , Liu Chenxi , Hu Wenbin
Published: September 2020

Purpose

This paper aims to study the effect of flow rate (0.42∼2.09 m/s) on the corrosion behavior of WB36CN1 steel pipe in the simulated secondary circuit water environment (170°C, 6 mg/L ethanolamine + 100 µg/L NaCl), for which an autoclave was used to simulate the secondary circuit environment for carrying out related experiments.

Design/methodology/approach

The corrosion behaviors were studied by electrochemical methods, morphological observations and elemental analysis.

Findings

As flow rate increases, the amplitude of the current noise fluctuates increased, noise resistance Rn and spectral noise resistance Rsn decreased, the shear stress on the surface of WB36CN1 steel increases, the oxygen content on the surface decreases, the roughness becomes smaller. Meanwhile, the energy of energy distribution plot is concentrated at high frequencies under the three flow conditions, the slopes of current power spectral density curve approach 0 db/decade. This means that the oxide on the surface becomes less and corrosion rate increases with increasing flow rate. The corrosion type of WB36CN1 steel was uniform corrosion; the degree of uniform corrosion is higher at high flow rate.

Originality/value

The effect of flow rate on the corrosion behavior of WB36CN1 steel pipe in the secondary circuit water environment was studied by using electrochemical methods in the laboratory. The effect mechanism of flow rate for corrosion behavior was obtained.
Acceptability and challenges of online higher education in the era of COVID-19: a study of students' perspective
Authors: Bisht Raj Kishor , Jasola Sanjay , Bisht Ila Pant
Published: September 2020

Purpose

Emergence of coronavirus disease 2019 (COVID-19) forced the world-wide education system to adopt online mode immediately. There are two main objectives of the paper: the first one is to know the acceptability of online mode of examination and learning amongst students by analysing the various aspects like difficulty, mental pressure, study pattern, etc. and the second one is to know the role of gender in adopting online education.

Design/methodology/approach

An online survey is conducted amongst the students of Graphic Era Hill University, Dehradun, India. Stratified sampling method has been used to select the students. First, a simple statistical analysis of the responses is conducted, and then chi-square test of independence has been used to know the dependency of various aspects on gender.

Findings

The two main findings of the present study are as follows: first, the online examinations were accepted with ease and low pressure in comparison to regular examination and second, the gender has a significant role in adopting online education with the observations that female students were more adoptable with online education in terms of assignments, study patterns and comfort. The present work also focuses on the challenges of online education like Internet connectivity, class interactions, etc.

Research limitations/implications

The present work was carried out during the initial time of pandemic in India when the focus was to continue the academic process by utilizing all the available resources in the absence of well-defined standards of online education.

Practical implications

The findings of the paper can be used for making strategies for online education across the world.

Social implications

The findings of the paper have shown that gender plays a significant role in adoptability of online education in Indian context.

Originality/value

The present work is conducted amid the environment of COVID-19. It reflects the analysis of students' responses towards the acceptability of online education under the difficult conditions developed due to the pandemic and subsequent lockdown.
Exploring the factors that mediate the relationship between entrepreneurial education and entrepreneurial intentions among undergraduate students in Ghana
Authors: Adu Isaac Nyarko , Boakye Kwame Owusu , Suleman Abdul-Razak , Bingab Bernard Bekuni Boawei
Published: September 2020

Purpose

The purpose of this paper is to propose and test a model to examine the factors that mediate the relationship between entrepreneurial education and entrepreneurial intentions among undergraduate students in Ghana. Specifically, the study identified entrepreneurial attitudes and behaviours (namely, risk-taking ability, self-efficacy, pro-activeness and behavioural control) that students ought to acquire through entrepreneurial education to increase their intentions to indulge in entrepreneurship.

Design/methodology/approach

The survey approach was adopted, with data collection done through administering questionnaires to students in the two public universities in the Central Region of Ghana. The model was tested using the partial least squares procedure.

Findings

The results found support for the proposed model, depicting that, with the exception of self-efficacy, other factors such as behavioural control, risk-taking ability and pro-activeness mediate the relationship between entrepreneurial education and entrepreneurial intentions of students.

Research limitations/implications

The major limitation of this study is that the proposed model was tested in only the public universities in the Central Region of Ghana. Subsequently, the validity of the model should be confirmed in other institutions.

Practical implications

The findings suggest that entrepreneurial education should be integrated into the course structure of all programmes across all disciplines in the tertiary institutions of Ghana. This will promote entrepreneurship and alleviate unemployment among university graduates.

Originality/value

The study provides a basis for tertiary institutions to develop programmes, policies and measures to help students to build upon their ability to take a risk, control their behaviour and be pro-active. This will influence their quest to become self-employed and not to rely on others and the government for employment after graduation.
Formal vs informal demand for credit by women in urban India: a comparative study in slums of Delhi and Mumbai
Authors: Malik Shruti , Maheshwari Girish Chandra , Singh Archana
Published: September 2020

Purpose

Over the period, the role of finance has emerged significant in the socio-economic development of the women. There are two major types of finances, i.e. formal and informal ones. Thus, the purpose of this paper is to investigate first the determinants of the demand for credit and then the demand for these credit sources by women especially in urban slums.

Design/methodology/approach

In this study, a primary survey was conducted with the help of a structured questionnaire in slums of two major urban cities in India, i.e. Delhi and Mumbai. In total, 450 individuals were interviewed in each city.

Findings

This paper presents a range of significant socio-economic factors affecting the demand for credit and source of credit by women borrower in Delhi and Mumbai. Despite, the greater emphasis by the government to increase the formal credit utilization, the informal credit is still preferred.

Practical implications

The outcomes of the study are expectedly useful to various policymakers and banks in encouraging women to opt more for the formal credit. The government can follow the research outcomes to scale up the programmes and schemes targeted for women empowerment in urban slums.

Originality/value

The study is unique of its kind in doing a comparative analysis in slums of two differently located urban cities with large slum population.
Knowledge mapping of hospital accreditation research: a coword analysis
Authors: Karamali Mazyar , Bahadori Mohammadkarim , Ravangard Ramin , Yaghoubi Maryam
Published: September 2020

Purpose

Hospital accreditation has been adopted internationally as a way and solution for healthcare quality improvement in hospitals. The purpose of this study was to review and knowledge mapping of bibliographic data about “Hospital Accreditation” and assess the current quantitative trends.

Design/methodology/approach

Scientometric methods and knowledge visualization using the coword analysis techniques conducted in three steps based on the data related to the field of hospital accreditation from 1975 to 2018 obtained from the MEDLINE database. Bibliographic data for titles, abstracts and keywords articles were saved in CSV format and MEDLINE templates by applying filters. Data extracted were exported into an Excel spreadsheet and were preprocessed. The authors applied the text mining and visualization using VOSviewer software.

Findings

Hospital accreditation studies have been increased rapidly over the past 30 years. 6,661 documents in the field of hospital accreditation had been published from 1975 to 2018. Hospitals or organizations active in the field of hospital accreditation were in the United States, Italy and Canada. The 10 most productive authors identified in the area of hospital accreditation with a higher influence were identified. “The United States”, “accreditation”, “Joint commission on accreditation” and “quality assurance, healthcare” had, respectively, the highest frequency. The cluster analysis identified and categorized them into four major clusters. Hospital accreditation field had a close relationship with the quality improvement, patient safety, risk and standards.

Originality/value

Hospital accreditation had focused on the scopes of implementation of accreditation programs, adherence to JCI standards, and focus on safety and quality improvement. Future studies are recommended to be conducted on design interventions and paying attention to all dimensions of hospital accreditation.