bluuebunny/crossref_metadata_2025 huggingface dataset:
Responsivity of the striatal dopamine system to methylphenidate – a within-subject I-123-ß-CIT-SPECT study in children and adolescents with Attention-Deficit/Hyperactivity Disorder
Authors: Aster Hans-Christoph , Romanos Marcel , Walitza Susanne , Gerlach Manfred , Mühlberger Andreas , Hasenauer Natalie , Hartrampf Philipp E. , Nerlich Kai , Reiners Christoph , Lorenz Reinhard , Buck Andreas K. , Deserno Lorenz
Published: November 2021

Background

Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight in how effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning.

Methods

Thirteen adolescent male patients (9-16 years) with diagnosis of ADHD according to DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-ß-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in on and off-MPH status balanced for order across participants. A virtual-reality continuous-performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH.

Results

On-MPH status was associated with a highly significant decrease (−27,6%) of striatal DAT BP as compared to off-MPH (t=4.93, p<0.001). More pronounced decrease in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r=0.68, p=0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings off-MPH (Pearson r=0.56, p=0.04). In further exploratory analysis in left vs. right striatal sub-regions, stronger decrease in DAT BP in the right caudate nucleus was weakly associated with improved performance in the continuous-performance test (Pearson r= - 0.54, p=0.07).

Conclusion

Our findings corroborate previous reports from mainly adult samples that MPH reduces striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity. More speculatively, regional specific responsivity of DAT BP to MPH may reflect treatment response with respect to cognitive functioning. However, implications from this small patient sample should be treated with caution and warrant replication.
Hypertonic saline and aprotinin based blockage of SARS-CoV-2 specific furin site cleavage by inhibition of nasal protease activity
Authors: Li Clarissa , Li Adam W.
Published: November 2021

SARS-CoV-2 enters into the human body mainly through the nasal epithelial cells. Cell entry of SARS-CoV-2 needs to be pre-activated by S1/S2 boundary furin motif cleavage by furin and/or relevant proteases. It is important to locally block SARS-CoV-2 S1/S2 site cleavage caused by furin and other relevant protease activity in the nasal cavity. We tested hypertonic saline and aprotinin-based blockage of SARS-CoV-2 specific furin site cleavage by furin, trypsin and nasal swab samples containing nasal proteases. Our results show that saline and aprotinin block SARS-Cov-2 specific furin site cleavage and that a saline and aprotinin combination could significantly reduce SARS-Cov-2 wild-type and P681R mutant furin site cleavage by inhibition of nasal protease activity.
The gendered self: Evidence for differences in whole-brain dynamics
Authors: Uribe Carme , Escrichs Anira , de Filippi Eleonora , Sanz-Perl Yonatan , Junque Carme , Gomez-Gil Esther , Kringelbach Morten L , Guillamon Antonio , Deco Gustavo
Published: November 2021

How the brain constructs gender identity is largely unknown, but some neural differences have recently been discovered. Here, we used an intrinsic-ignition framework to investigate if gender identity changes the propagation of the neural activity across the whole-brain network and within resting-state networks. Studying 29 transmen and 17 transwomen with gender incongruence, 22 ciswomen, and 19 cismen, we computed the capability of a given brain area in space to propagate activity to other areas (mean-ignition) and its variability across time (node-metastability). We found that both measures differentiated all four groups across the whole-brain network. Furthermore, at the network level, we found that compared to the other groups, cismen showed higher mean-ignition of the dorsal attention network and node-metastability of the dorsal and ventral attention, executive control, and temporal parietal networks. We also found mean-ignition differences between cismen and ciswomen within the executive control network, but higher in ciswomen than cismen and transmen for the default-mode network. For the node-metastability, this was higher in cismen compared to ciswomen in the somatomotor network, while both mean-ignition and node-metastability were higher for cismen than transmen in the limbic network. Finally, we computed correlations between both measures and their body image scores. Transmen dissatisfaction, cismen, and ciswomen satisfaction towards their own body image were distinctively associated with specific networks per group. Overall, the study of the whole-brain network dynamical complexity discriminates binary gender identity groups, and functional connectivity dynamics approaches are needed to disentangle the complex understanding of the gendered self.

Significance statement

The study of sex/gender differences may be enriched by the heterogeneity of other gender minority groups, such as transgender. Functional connectivity measures capturing the spatio-temporal oscillations of the brain can provide insights on how the brain cooperates. This is the first study investigating how the whole-brain network propagates information across the brain, spatially and temporally, in binary gender groups (cisgender and transgender) by means of the intrinsic-ignition framework. We found four whole-brain unique phenotypes pertaining to each gender group, namely cismen, ciswomen, transmen and transwomen. Novel functional connectivity dynamics frameworks can contribute to disentangle the complex experience of agendered-self.
Acute SARS-CoV-2 infection in pregnancy is associated with placental ACE-2 shedding
Authors: Taglauer Elizabeth S. , Wachman Elisha M. , Juttukonda Lillian , Klouda Timothy , Kim Jiwon , Wang Qiong , Ishiyama Asuka , Hackam David J. , Yuan Ke , Jia Hongpeng
Published: November 2021

Human placental tissues have variable rates of SARS-CoV-2 invasion resulting in consistently low rates of fetal transmission suggesting a unique physiologic blockade against SARS-CoV-2. Angiotensin-converting enzyme (ACE)-2, the main receptor for SARS-CoV-2, is expressed as cell surface and soluble forms regulated by a metalloprotease cleavage enzyme, ADAM17. ACE-2 is expressed in the human placenta, but the regulation of placental ACE-2 expression in relation to timing of maternal SARS-CoV-2 infection in pregnancy is not well understood. In this study, we evaluated ACE-2 expression, ADAM17 activity and serum ACE-2 abundance in a cohort of matched villous placental and maternal serum samples from Control pregnancies (SARS-CoV-2 negative, n=8) and pregnancies affected by symptomatic maternal SARS-CoV-2 infections in the 2nd trimester (“2ndTri COVID”, n=8) and 3rd trimester (“3rdTri COVID”, n=8). In 3rdTri COVID as compared to control and 2ndTri-COVID villous placental tissues ACE-2 mRNA expression was remarkably elevated, however, ACE-2 protein expression was significantly decreased with a parallel increase in ADAM17 activity. Soluble ACE-2 was also significantly increased in the maternal serum from 3rdTri COVID infections as compared to control and 2ndTri-COVID pregnancies. These data suggest that in acute maternal SARS-CoV-2 infections, decreased placental ACE-2 protein may be the result of ACE-2 shedding. Overall, this work highlights the importance of ACE-2 for ongoing studies on SARS-CoV-2 responses at the maternal-fetal interface.
Is Footedness Driving Right Lower Extremity Arthroplasty Becoming Commoner Than Left Lower Extremity Arthroplasty?
Authors: Gupta Deepak
Published: November 2021

The question arises whether footedness transforms into asymmetrical incidence of wear and tear within lower extremity joints. After obtaining institutional review board approval for exempt research, the author manually counted the number of patients who underwent right or left or bilateral, hip or knee, primary or revision arthroplasty over a five-year period (2016-2020) at a university-affiliated hospital in the United States. Overall, right lower extremity arthroplasty was significantly commoner than left lower extremity arthroplasty (P=0.002). Individually, only right primary hip arthroplasty (P=0.033) and right revision knee arthroplasty (P=0.041) were significantly commoner procedures than their left counterparts. These results should set up the stage for future investigations into footedness retrospectively and prospectively to rule out if commoner right footedness in itself is driving this asymmetrical incidence of lower extremity arthroplasty or whether automatic transmission vehicular driving is independently contributing to this asymmetrical incidence.
Genomic regions associated with chocolate spot (Botrytis fabaeSard.) resistance in faba bean (Vicia fabaL.)
Authors: Gela Tadesse S. , Bruce Margaret , Chang Wei , Stoddard Frederick L. , Schulman Alan H. , Vandenberg Albert , Khazaei Hamid
Published: November 2021

Chocolate spot (CS), caused byBotrytis fabaeSard., is an important threat to global faba bean production. Growing resistant faba bean cultivars is, therefore, paramount to preventing yield loss. To date, there have been no reported quantitative trait loci (QTLs) associated with CS resistance in faba bean. The objective of this study was to identify genomic regions associated with CS resistance using a recombinant inbred line (RIL) population derived from resistant accession ILB 938. A total of 165 RILs from the cross Mélodie/2 × ILB 938/2 were genotyped and evaluated for CS reactions under replicated controlled climate conditions. QTL analysis identified five loci contributing to CS resistance on faba bean chromosomes 1 and 6, accounting for 5.0–23.4% of the total phenotypic variance. The sequences of SNP markers linked to resistance QTLs on chromosome 1 that have the largest effects encode multiple classes of putative disease and/or defense-related genes. The results of this study not only provide insight into disease-resistance QTLs, but also can be used as potential targets for marker-assisted breeding in faba bean genetic improvement for CS resistance.

Key message

QTL mapping identified key genomic regions associated with chocolate spot resistance on faba bean chromosomes 1 and 6, which may serve as novel genetic tools to develop disease-resistant faba bean cultivars.
Inhibition of the TLR4 signalling pathway with TAK-242 reduces RSV infection and cytokine release in primary airway epithelial cells
Authors: Broadbent Lindsay , Roberts Grace C. , Coey Jonathon D. , Barabas Judit , Shields Michael D. , Power Ultan F. ,   the Breathing Together Consortium
Published: November 2021

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalisation in children worldwide, but there is still no vaccine or anti-viral treatment available. RSV has been implicated in the development of respiratory diseases such as asthma. Toll like receptor 4 (TLR4) has been well characterised in the immune responses to RSV. However, the role of TLR4 in RSV infection remains unclear. To study RSV in the lung epithelium, where RSV preferentially infects ciliated cells, we used a well-differentiated primary airway epithelial cell (WD-PAEC) model: a pseudostratified epithelium that produces mucus and beating cilia. We demonstrate in this physiologically relevant model that TLR4 is a pro-viral factor. Inhibition of TLR4 using TAK-242 significantly reduces RSV titres in WD-PAECs in a dose-dependent manner but has no effect on RSV growth kinetics in a range of immortalised respiratory-derived cell lines. Specific inhibition of a range of downstream effectors of TLR4 signalling in the WD-PAEC model identified p38 MAPK as a pro-viral factor, whereas inhibition of MEK1/2 significantly increased RSV titres. Our data demonstrate a role for TLR4 in RSV infection and highlight the importance of biologically relevant models to study virus-host interactions.

Author summary

Respiratory Syncytial Virus (RSV) can cause severe respiratory infection in young children and is responsible for approximately 200,000 deaths worldwide every year. Despite decades of research since the identification of this virus in the 1950s there is still no vaccine or treatment available. Advances in research have led to the development of cell cultures that are very similar to the cells that line human airways. These cultures provide an opportunity to study how viruses interacts with airway cells in a representative model and may provide insights that traditional research models have not yet been able to answer. Using this experimental model we show that a drug, TAK-242 which targets a pathogen recognition receptor on the surface of cells, reduces growth of RSV and dampens the immune response to infection in these airway cells. Our data demonstrate potential targets for RSV treatments and also highlight the importance of using relevant experimental models.
Genome-wide association studies and genomic selection assays made in a large sample of cacao (Theobroma cacaoL.) germplasm reveal significant marker-trait associations and good predictive value for improving yield potential
Authors: Bekele Frances L. , Bidaisee Gillian G. , Allegre Mathilde , Argout Xavier , Fouet Olivier , Boccara Michel , Saravanakumar Duraisamy , Bekele Isaac , Lanaud Claire
Published: November 2021

A genome-wide association study was undertaken to unravel marker-trait associations (MTAs) between SNP markers and yield-related traits. It involved a subset of 421 cacao accessions from the large and diverse collection conservedex situat the International Cocoa Genebank Trinidad. An average linkage disequilibrium (r2) of 0.10 at 5.2 Mb was found across several chromosomes. Seventeen significant (P≤ 8.17 × 10-5(–log10 (p) = 4.088)) MTAs of interest, which accounted for 5 to 17% of the explained phenotypic variation, were identified using a Mixed Linear Model in TASSEL version 5.2.50. The most significant MTAs identified were related to seed number and seed length on chromosome 7 and seed number on chromosome 1. Other significant MTAs involved seed length to width ratio on chromosomes 3 and 5 and seed length on chromosomes 4 and 9. It was noteworthy that several yield-related traits,viz., seed length, seed length to width ratio and seed number were associated with markers on different chromosomes, indicating their polygenic nature. Approximately 40 candidate genes that encode embryo and seed development, protein synthesis, carbohydrate transport and lipid biosynthesis and transport were identified in this study. A significant association of fruit surface anthocyanin intensity co-localised with MYB-related protein 308 on chromosome 4. Testing of a genomic selection approach revealed good predictive value (GEBV) for economic traits such as seed number (GEBV = 0.611), seed length (0.6199), seed width (0.5435), seed length to width ratio (0.5503), seed/cotyledon mass (0.6014) and ovule number (0.6325). The findings of this study could facilitate genomic selection and marker-assisted breeding of cacao thereby expediting improvement in the yield potential of cacao planting material.
NGSpop: A desktop software that supports population studies by identifying sequence variations from next-generation sequencing data
Authors: Lee Dong-Jun , Kwon Taesoo , Lee Hye-Jin , Oh Yun-Ho , Kim Jin-Hyun , Lee Tae-Ho
Published: November 2021

Next-generation sequencing (NGS) is widely used in all areas of genetic research, such as for genetic disease diagnosis and breeding, and it can produce massive amounts of data. The identification of sequence variants is an important step when processing large NGS datasets; however, currently, the process is complicated, repetitive, and requires concentration, which can be taxing on the researcher. Therefore, to support researchers who are not familiar with bioinformatics in identifying sequence variations regularly from large datasets, we have developed a fully automated desktop software, NGSpop. NGSpop includes functionalities for all the variant calling and visualization procedures used when processing NGS data, such as quality control, mapping, filtering details, and variant calling. In the variant calling step, the user can select the GATK or DeepVariant algorithm for variant calling. These algorithms can be executed using pre-set pipelines and options or customized with the user-specified options. NGSpop is implemented using JavaFX (version 1.8) and can thus be run on Unix like operating systems such as Ubuntu Linux (version 16.04, 18.0.4). Although there are several pipelines and visualization tools available for NGS data analysis, most integrated environments do not support batch processes; thus, variant detection cannot be automated for population-level studies. The NGSpop software, developed in this study, has an easy-to-use interface and helps in rapid analysis of multiple NGS data from population studies.
Biomechanical characteristics of scapula and glenohumeral movements during pitching motion in injury-prone college baseball pitchers
Authors: Miyashita Koji , Koshida Sentaro , Koyama Taro , Ota Kenicihro , Tani Yusuke , Okamune Ryoji
Published: November 2021

Coordination of glenohumeral and scapular movements plays an important role in the injury prevention of baseball pitchers. However, there is no objective data establishing the direct relationship between pitching injuries and associated glenohumeral and scapular movements. Therefore, the objectives of the present study were to demonstrate biomechanical differences in scapular and glenohumeral movements during pitching between injury-prone pitchers and healthy college baseball pitchers. Thirty collegiate baseball pitchers were classified into two groups according to their injury status: injury-prone group (N=15, 20.7±1.4 years, 180.1±6.5 cm, 78.9±5.4 kg) and control group (N=15, 20.9±1.1 years, 177.1±6.6 cm, 72.3±6.7 kg). We obtained the pitching motion data using the three-dimensional motion analysis technique with four high-speed cameras. The horizontal abduction angles of the glenohumeral joint during cocking and acceleration phases were significantly greater in injury-prone pitchers [19.0° (95% CI: 14.4–23.6) at foot contact, −4.0° (95% CI: −7.7 to −0.2) at maximum external rotation (MER), and −0.3° (95% CI: −4.8 to −4.2) at ball release] than in healthy controls [11.7 °(95%CI:7.1 to 16.3) at foot contact, −10.0°(95%CI: −13.7 to −6.3) at MER, and −6.9°(95%CI: −11.4 to −2.4)](p<0.01). In addition, the external rotation angle (ER) of the scapula at MER was significantly greater in the injury-prone group [−0.1° (95% CI: −5.0 to 4.8)] than in the control group [−12.3° (95% CI: −17.2 to −7.4)] (p<0.01), but there was no difference in the scapular ER during foot contact between the two groups. These results suggests that injury-prone pitchers have less internal rotation of the scapula and more horizontal abduction of the glenohumeral joint during cocking and acceleration phases. Therefore, sports medicine practitioners may need to pay more attention to coordination of scapular and glenohumeral movements during the cocking and acceleration phases of pitching for prevention of shoulder injuries.
Adaptive coding of stimulus information in human frontoparietal cortex during visual classification
Authors: Wisniewski David , González-García Carlos , Formica Silvia , Woolgar Alexandra , Brass Marcel
Published: November 2021

The neural mechanisms of how frontal and parietal brain regions support flexible adaptation of behavior remain poorly understood. Here, we used functional magnetic resonance imaging (fMRI) and model-based representational similarity analysis (RSA) to investigate frontoparietal representations of stimulus information during visual classification under varying task demands. Based on prior research, we predicted that increasing perceptual task difficulty should lead to more categorical coding of stimulus information, and that exemplar-level stimulus coding would be restricted to posterior, sensory brain regions. Counter to our expectations, however, we found frontoparietal regions encoded exemplar-level stimulus information. Interestingly, the anterior intraparietal sulcus (aIPS) encoded stimuli equally well regardless of perceptual difficulty, and these representations were directly related to choice behavior (proportion of guessing). Overall, these findings reveal unexpected exemplar-level stimulus coding in frontoparietal cortex, and highlight the role of aIPS in supporting adaptive behavior.
Quantification of vascular networks in photoacoustic mesoscopy
Authors: Brown Emma L. , Lefebvre Thierry L. , Sweeney Paul W. , Stolz Bernadette J. , Gröhl Janek , Hacker Lina , Huang Ziqiang , Couturier Dominique-Laurent , Harrington Heather A. , Byrne Helen M. , Bohndiek Sarah E.
Published: November 2021

Mesoscopic photoacoustic imaging (PAI) enables non-invasive visualisation of tumour vasculature and has the potential to assess prognosis and therapeutic response. Currently, evaluating vasculature using mesoscopic PAI involves visual or semi-quantitative 2D measurements, which fail to capture 3D vessel network complexity, and lack robust ground truths for assessment of segmentation accuracy. Here, we developed anin silico, phantom,in vivo, andex vivo-validated end-to-end framework to quantify 3D vascular networks captured using mesoscopic PAI. We applied our framework to evaluate the capacity of rule-based and machine learning-based segmentation methods, with or without vesselness image filtering, to preserve blood volume and network structure by employing topological data analysis. We first assessed segmentation performance against ground truth data ofin silicosynthetic vasculatures and a photoacoustic string phantom. Our results indicate that learning-based segmentation best preserves vessel diameter and blood volume at depth, while rule-based segmentation with vesselness image filtering accurately preserved network structure in superficial vessels. Next, we applied our framework to breast cancer patient-derived xenografts (PDXs), with correspondingex vivoimmunohistochemistry. We demonstrated that the above segmentation methods can reliably delineate the vasculature of 2 breast PDX models from mesoscopic PA images. Our results underscore the importance of evaluating the choice of segmentation method when applying mesoscopic PAI as a tool to evaluate vascular networksin vivo.
Influenza A virus hemagglutinin prevents extensive membrane damage upon dehydration
Authors: Iriarte-Alonso Maiara A. , Bittner Alexander M. , Chiantia Salvatore
Published: November 2021

While the molecular mechanisms of virus infectivity are rather well known, the detailed consequences of environmental factors on virus biophysical properties are poorly understood. Seasonal influenza outbreaks are usually connected to the low winter temperature, but also to the low relative air humidity. Indeed, transmission rates increase in cold regions during winter. While low temperature must slow degradation processes, the role of low humidity is not clear. We studied the effect of relative humidity on a model of influenza A H1N1 virus envelope, a supported lipid bilayer containing the surface glycoprotein hemagglutinin (HA), which is present in the viral envelope in very high density. For complete cycles of hydration, dehydration and rehydration, we evaluate the membrane properties in terms of structure and dynamics, which we assess by combining confocal fluorescence microscopy, raster image correlation spectroscopy, line-scan fluorescence correlation spectroscopy and atomic force microscopy. Our findings indicate that the presence of HA prevents macroscopic membrane damage after dehydration. Without HA, fast membrane disruption is followed by irreversible loss of lipid and protein mobility. Although our model is principally limited by the membrane composition, the macroscopic effects of HA under dehydration stress reveal new insights on the stability of the virus at low relative humidity.
Correlations from structure and phylogeny combine constructively in the inference of protein partners from sequences
Authors: Gerardos Andonis , Dietler Nicola , Bitbol Anne-Florence
Published: November 2021

Inferring protein-protein interactions from sequences is an important task in computational biology. Recent methods based on Direct Coupling Analysis (DCA) or Mutual Information (MI) allow to find interaction partners among paralogs of two protein families. Does successful inference mainly rely on correlations from structural contacts or from phylogeny, or both? Do these two types of signal combine constructively or hinder each other? To address these questions, we generate and analyze synthetic data produced using a minimal model that allows us to control the amounts of structural constraints and phylogeny. We show that correlations from these two sources combine constructively to increase the performance of partner inference by DCA or MI. Furthermore, signal from phylogeny can rescue partner inference when signal from contacts becomes less informative, including in the realistic case where inter-protein contacts are restricted to a small subset of sites. We also demonstrate that DCA-inferred couplings between non-contact pairs of sites improve partner inference in the presence of strong phylogeny, while deteriorating it otherwise. Moreover, restricting to non-contact pairs of sites preserves inference performance in the presence of strong phylogeny. In a natural data set, as well as in realistic synthetic data based on it, we find that non-contact pairs of sites contribute positively to partner inference performance, and that restricting to them preserves performance, evidencing an important role of phylogeny.

Author summary

In protein sequence data, the amino acid usages at different sites of a protein or of two interacting proteins can be correlated because of functional constraints. For instance, the need to maintain physicochemical complementarity among two sites that are in contact in the three-dimensional structure of a protein complex causes such correlations. However, correlations can also arise due to shared evolutionary history, even in the absence of any functional constraint. While these phylogenetic correlations are known to obscure the inference of structural contacts, we show, using controlled synthetic data, that correlations from structure and phylogeny combine constructively to allow the inference of protein partners among paralogs using just sequences. We also show that pairs of amino acids that are not in contact in the structure have a major impact on partner inference in a natural data set and in realistic synthetic ones. These findings explain the success of methods based on pairwise maximum-entropy models or on information theory at predicting protein partners from sequences among paralogs.
Local adaptation mediated niche expansion in correlation with genetic richness
Authors: Kurokawa Masaomi , Nishimura Issei , Ying Bei-Wen
Published: November 2021

As a central issue in evolution and ecology, the quantitative relationship among the genome, adaptation and the niche was investigated. Local adaptation of five Escherichia coli strains carrying either the wild-type genome or reduced genomes was achieved by experimental evolution. A high-throughput fitness assay of the ancestor and evolved populations across an environmental gradient of eight niches resulted in a total of 80 fitness curves generated from 2,220 growth curves. Further analyses showed that the increases in both local adaptiveness and niche broadness were negatively correlated with genetic richness. Local adaptation caused common niche expansion, whereas niche expansion for generality or speciality was decided by genetic richness. The order of the mutations accumulated stepwise was correlated with the magnitude of the fitness increase attributed to mutation accumulation. Pre-adaptation probably participated in coordination among genetic richness, local adaptation and niche expansion.
IReNA: integrated regulatory network analysis of single-cell transcriptomes and chromatin accessibility profiles
Authors: Jiang Junyao , Lyu Pin , Li Jinlian , Huang Sunan , Blackshaw Seth , Qian Jiang , Wang Jie
Published: November 2021

Although single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) have been widely used, few methods can reliably integrate these data to perform regulatory network analysis. Here, we developed IReNA (Integrated Regulatory Network Analysis) for network inference through integrated analysis of scRNA-seq and scATAC-seq data, network modularization, transcription factor enrichment, and construction of simplified intermodular regulatory networks. Using public datasets, we showed that integrated network analysis of scRNA-seq and scATAC-seq data using IReNA outperformed currently available methods in identifying known regulators. IReNA facilitates the systems-level understanding of biological regulatory mechanisms, and is available at https://github.com/jiang-junyao/IReNA.
Genome-wide mapping of histone modification H3K4me3 in bovine oocytes and early embryos
Authors: Dang Yanna , Luo Lei , Shi Yan , Li Shuang , Wang Shaohua , Zhang Kun
Published: November 2021

Reprogramming of histone modifications is critical to safeguard correct gene expression profile during preimplantation development. Of interest, trimethylation of lysine 4 on histone 3 (H3K4me3) exhibits a unique and dynamic landscape with a potential species-specific feature. Here, we address how it is reprogrammed and its functional significance during oocyte maturation and early embryonic development in cows. Notably, the overall signal of H3K4me3 decreased sharply during embryonic genome activation (EGA). By using low input ChIP-seq technology, we find widespread broad H3K4me3 domains in oocytes and early cleaved embryos. The broad domains are gradually removed after fertilization, which is obviously seen during EGA. Meanwhile, H3K4me3 become enriched at promoter regions. Interestingly, the gene expression level displays a positive correlation with the relative H3K4me3 signal of their promoters when embryos reach 16-cell stage. Importantly, disruption of H3K4me3 demethylases KDM5A-5C increases H3K4me3 level, decreases the embryonic developmental rate and results in dysregulation of over a thousand genes. Meanwhile, KDM5 deficiency causes a re-destribution of H3K4me3 across genome. In particular, the positive correlation between promoter H3K4me3 enrichment and gene expression level disappear. Overall, we describe the genomic reprogramming of H3K4me3 in a greater resolution during bovine preimplantation development and propose that KDM5-mediated re-distribution of H3K4me3 plays an important role in modulating oocyte-to-embryonic transition.
Parent-offspring inference in inbred populations
Authors: Runge Jan-Niklas , König Barbara , Lindholm Anna K. , Bendesky Andres
Published: November 2021

Genealogical relationships are fundamental components of genetic studies. However, it is often challenging to infer correct and complete pedigrees even when genome-wide information is available. For example, inbreeding can obfuscate genetic differences between individuals, making it difficult to even distinguish first-degree relatives such as parent-offspring from full siblings. Similarly, genotyping errors can interfere with the detection of genetic similarity between parents and their offspring. Inbreeding is common in natural, domesticated, and experimental populations and genotyping of these populations often has more errors than in human datasets, so efficient methods for building pedigrees under these conditions are necessary. Here, we present a new method for parent-offspring inference in inbred pedigrees called SPORE (Specific Parent-Offspring Relationship Estimation). SPORE is vastly superior to existing pedigree-inference methods at detecting parent-offspring relationships, in particular when inbreeding is high or in the presence of genotyping errors, or both. SPORE therefore fills an important void in the arsenal of pedigree inference tools.

Author Summary

Knowing the genealogical relationships among individuals is critical for genetic analyses, such as for identifying the mutations that cause diseases or that contribute to valuable agricultural traits such as milk production. Although many tools exist for establishing pedigrees using genetic information, these tools fail when individuals are highly inbred, such as in domesticated animals, or in groups of people in which consanguineous matings are common. Furthermore, existing tools do not work well when genetic information has errors at levels observed in modern datasets. Here, we present a novel approach to solve these problems. Our method is significantly more accurate than existing tools and more tolerant of errors in the genetic data. We expect that our method, which is simple to use and computationally efficient, will be a useful tool in a diversity of settings, from the studies of human and natural populations, to agricultural and experimental settings.
iEnhancer-CLA: Self-attention-based interpretable model for enhancers and their strength prediction
Authors: Cai Lijun , Ren Xuanbai , Fu Xiangzheng , Gao Mingyu , Wang Peng , Xu Junling , Liu Wei , Li Zejun , Zeng Xiangxiang
Published: November 2021

Enhancer is a class of non-coding DNA cis-acting elements that plays a crucial role in the development of eukaryotes for their transcription. Computational methods for predicting enhancers have been developed and achieve satisfactory performance. However, existing computational methods suffer from experience-based feature engineering and lack of interpretability, which not only limit the representation ability of the models to some extent, but also make it difficult to provide interpretable analysis of the model prediction findings.In this paper, we propose a novel deep-learning-based model, iEnhancer-CLA, for identifying enhancers and their strengths. Specifically, iEnhancer-CLA automatically learns sequence 1D features through multiscale convolutional neural networks (CNN), and employs a self-attention mechanism to represent global features formed by multiple elements (multibody effects). In particular, the model can provide an interpretable analysis of the enhancer motifs and key base signals by decoupling CNN modules and generating self-attention weights. To avoid the bias of setting hyperparameters manually, we construct Bayesian optimization methods to obtain model global optimization hyperparameters. The results demonstrate that our method outperforms existing predictors in terms of accuracy for identifying enhancers and their strengths. Importantly, our analyses found that the distribution of bases in enhancers is uneven and the base G contents are more enriched, while the distribution of bases in non-enhancers is relatively even. This result contributes to the improvement of prediction performance and thus facilitates revealing an in-depth understanding of the potential functional mechanisms of enhancers.

Author summary

The enhancers contain many subspecies and the accuracy of existing models is difficult to improve due to the small data set. Motivated by the need for accurate and efficient methods to predict enhancer types, we developed a self-attention deep learning model iEnhancer-CLA, the aim is to be able to distinguish effectively and quickly between subspecies of enhancers and whether they are enhancers or not. The model is able to learn sequence features effectively through the combination of multi-scale CNN blocks, BLSTM layers, and self-attention mechanisms, thus improving the accuracy of the model. Encouragingly, by decoupling the CNN layer it was found that the layer was effective in learning the motif of the sequences, which in combination with the self-attention weights could provide interpretability to the model. We further performed sequence analysis in conjunction with the model-generated weights and discovered differences in enhancer and non-enhancer sequence characteristics. This phenomenon can be a guide for the construction of subsequent models for identifying enhancer sequences.
Identifying and cultivating voluntary helpful employee behavior
Authors: Lyons Paul , Bandura Randall , Levitt Kenneth J.
Published: November 2021

Purpose

This essay is practitioner-focused and aims to provide the manager or supervisor with a summary of critical information regarding voluntary, employee helpful behavior or organizational citizenship behavior (OCB). The summary helps explain motivation and predispositions per OCB, as well as explicit advice regarding ways to encourage and, perhaps, recognize this desired behavior.

Design/methodology/approach

Methodology is grounded on two elements. First, a literature review of empirical and other research on OCB, pro-social behavior, extra-role behavior, and contextual performance. Second, based on review and brief analysis of features of the behavior to include: definitions, motivation/predispositions, and employee performance, explicit guidance is offered for managers.

Findings

Critical information is provided about OCB and voluntary helpful behavior. The objective is to identify important aspects of the behavior and place it in a format that is accessible to the typical manager or supervisor. This approach can assist the manager to create appropriate means to identify the desired behavior as well as to encourage it.

Practical implications

Virtually all of the empirical research on OCB and other forms of voluntary helpful behavior make the case that such behavior is most desirable for the organization, manager, and co-workers. The research also points out that not all employees who engage in the behavior have expectations of recognition or any form of reward for their actions. This essay gives the practitioner information regarding observation of the behavior and its motivation. In addition, advice is provided to assist in stimulating the desired behavior.

Originality/value

Currently, nearly all of the expressions of OCB and voluntary helpful employee behavior are found in academic journals and related literature. Typically, these sources of information are not readily available to practicing managers. This condition is what prompts an essay aimed at practitioners that captures the essential aspects of the voluntary, desirable employee behavior as well as practical advice.
Using data mining to track the information spreading on social media about the COVID-19 outbreak
Authors: Xing Yunfei , He Wu , Cao Gaohui , Li Yuhai
Published: November 2021

Purpose

COVID-19, a causative agent of the potentially fatal disease, has raised great global public health concern. Information spreading on the COVID-19 outbreak can strongly influence people behaviour in social media. This paper aims to question of information spreading on COVID-19 outbreak are addressed with a massive data analysis on Twitter from a multidimensional perspective.

Design/methodology/approach

The evolutionary trend of user interaction and the network structure is analysed by social network analysis. A differential assessment on the topics evolving is provided by the method of text clustering. Visualization is further used to show different characteristics of user interaction networks and public opinion in different periods.

Findings

Information spreading in social media emerges from different characteristics during various periods. User interaction demonstrates multidimensional cross relations. The results interpret how people express their thoughts and detect topics people are most discussing in social media.

Research limitations/implications

This study is mainly limited by the size of the data sets and the unicity of the social media. It is challenging to expand the data sets and choose multiple social media to cross-validate the findings of this study.

Originality/value

This paper aims to find the evolutionary trend of information spreading on the COVID-19 outbreak in social media, including user interaction and topical issues. The findings are of great importance to help government and related regulatory units to manage the dissemination of information on emergencies, in terms of early detection and prevention.
Omnichannel retailing: does it empower consumers and influence patronage?
Authors: Mishra Sita , Malhotra Gunjan , Arora Vibha , Mukhopadhyay Sandip
Published: November 2021

Purpose

This study analyzes how omnichannel integration influences customer patronage intention, highlighting the moderation effect of consumer service experience consciousness. Additionally, it also examines the sequential mediating role of consumer empowerment and satisfaction.

Design/methodology/approach

This study uses a survey method to collect data from 336 young Indian consumers, having experienced omnichannel retailing. Data were analyzed using SPSS PROCESS macro to examine both the mediating and moderated relationships.

Findings

The results confirm that a customers' perceived online–offline channel integration increases their patronage intention directly and through the mediating role of consumer empowerment and satisfaction. Additionally, as a moderator, consumer service experience consciousness does not necessarily impact consumer patronage interest through the mediating role of consumer empowerment. Nevertheless, it does have a negative impact through the mediating role of consumer satisfaction.

Practical implications

This study provides insights into designing online–offline retailing integration, based upon which, proposes several recommendations for increasing customer satisfaction and patronage intention.

Originality/value

To the best of the authors' knowledge, this is among the first studies to highlight the theory of consumer empowerment in the context of omnichannel retailing. Thus, it contributes to the extant literature on omnichannel retailing while investigating the moderating role of consumer service experience consciousness.
Multi-objective maintenance planning under preventive maintenance
Authors: Al-Refaie Abbas , Almowas Hiba
Published: November 2021

Purpose

This research developed and examined a mathematical model for concurrent corrective and preventive maintenance policy of a system of series configuration.

Design/methodology/approach

A mathematical model was developed to maximize availability, and maximal net revenues, and minimal cost. Different probability distributions for time to failure and time to repair were considered. The model was then implemented on a real case study, which was studied under corrective maintenance policy and concurrent corrective and preventive policy.

Findings

A comparison between results at current policy (90 days) and optimal period of corrective and preventive policy was conducted. It was found that availability, profit was increased from 94.4% and $20.091 – 96.5% and $24.803, respectively. Further, the cost was reduced from $1104.8 to $797.22.

Research limitations/implications

The proposed optimization model can be adopted in planning maintenance activities for a single machine as well as for a system of series configuration machines under various probability distributions.

Practical implications

The proposed model can significantly enhance performance of the production as well as maintenance systems. In addition, the developed model may support maintenance engineering in effective management of maintenance resources and the performance of its activities.

Originality/value

This research considers a mathematical model with multi-objective functions and distinct probability distributions for time-to-failure for a system of series machines. Moreover, appropriate approximation solution was deployed to find integral of some functions. Finally, it provides maintenance planning for a single machine or a series of machines.
Network Mechanisms in the Entry and Post‐Entry Phases of Internationalization: Evidence from Finnish Family Firms
Authors: Leppäaho Tanja , Jack Sarah L. , Plakoyiannaki Emmanuella
Published: November 2021

In this study, we posed the questions: (i) What network mechanisms do family firms (FFs) use in their entry and post‐entry? (ii) How do they use these network mechanisms? (iii) Why do they use these mechanisms? We based our study on social network theory, and on two opposing network mechanisms,network closureandstructural holes, referring also to research on FFs and international networking. Applying a multiple case design with 15 Finnish FFs, we identified four types of FFs – trotter, preserver, explorer and conqueror – based on how they used their network mechanisms at entry and post‐entry. We offer a new mechanism that we labelnetwork terminationand explain the heterogeneous networking behaviour of the investigated cases. During post‐entry, bifurcation‐biased FFs used network mechanisms differently from FFs that were able to rely on non‐family relational assets. The study contributes to social network theory, and sheds light on FF heterogeneity in the context of international networking.
The Phonetics and Phonology of Old Armenian , , and Prevocalic *
Authors: Kim Ronald I.
Published: November 2021

The Old Armenian letters  and  occur in nearly complementary distribution, but a century of scholarship has failed to resolve whether they denote separate phonemes, allophones, or allographs. The relation of these sounds to the vowel /u/ and interpretation of prevocalic  spellings are also debated. It is argued that Old Armenian had a single phoneme /u/ realized as [u] in syllabic positions, i.e. between consonants or between consonant and word boundary, and [w] or [v] next to a vowel. In initial position the nonsyllabic allophone was realized as [v], including before [ə] < pretonic *i, e.g.vasn[ˈvɑsən] ‘because of, with respect to’,vnas[vəˈnɑs] ‘harm, damage’, underyingly /uasn/, /uinas/. In word‐medial position the realization was [w] or perhaps [ʋ], which was written  afteroand  after other vowels. After a consonant,  occurs in the oblique case forms ofwo‐ andwo/ea‐stems, where it reflects dissimilation in the sequence *‐iyo‐> *‐yo‐> *‐wo‐; otherwise we find  representing [əw], e.g. inlowanam[ləwɑˈnɑm] ‘wash’, gen.anowan[ɑnəˈwɑn] ‘name’, underlyingly /luanam/, /anuan/. The diphthongsaw,ew,iw,ovcan therefore be interpreted as sequences of vowel + /u/, as int‘iw/t‘iu/ ‘number’, gen.t‘owoy/t‘iuoy/.