bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular spatial transcriptomics identifies three mechanistically different classes of localizing RNAs
Authors: Cassella Lucia , Ephrussi Anne
Published: December 2021

Intracellular RNA localization is a widespread and dynamic phenomenon that compartmentalizes gene expression and contributes to the functional polarization of cells. Thus far, mechanisms of RNA localization identified in Drosophila have been based on a few RNAs in different tissues, and a comprehensive mechanistic analysis of RNA localization in a single tissue is lacking. Here, by subcellular spatial transcriptomics we identify RNAs localized in the apical and basal domains of the columnar follicular epithelium (FE) and we analyze the mechanisms mediating their localization. Whereas the dynein/BicD/Egl machinery controls apical RNA localization, basally-targeted RNAs require kinesin-1 to overcome a “default” dynein-mediated transport. Moreover, a non-canonical, translation- and dynein-dependent mechanism mediates apical localization of a subgroup of dynein-activating adaptor RNAs (BicD, Bsg25D, hook). Altogether, our study identifies at least three mechanisms underlying RNA localization in the FE, and suggests a possible link between RNA localization and dynein/dynactin/adaptor complex formation in vivo.
Utilizing occupancy-detection models with museum specimen data: promise and pitfalls
Authors: Shirey Vaughn , Khelifa Rassim , M’Gonigle Leithen K. , Guzman Laura Melissa
Published: December 2021

Historical museum records provide potentially useful data for identifying drivers of change in species occupancy. However, because museum records are typically obtained via many collection methods, methodological developments are needed in order to enable robust inferences. Occupancy-detection models, a relatively new and powerful suite of methods, are a potentially promising avenue because they can account for changes in collection effort through space and time. Here we present a methodological road-map for using occupancy models to analyze historical museum records. We use simulated data-sets to identify how and when patterns in data and/or modelling decisions can bias inference. We focus primarily on the consequences of contrasting methodological approaches for dealing with species’ ranges and inferring species’ non-detections in both space and time. We find that not all data-sets are suitable for occupancy-detection analysis but, under the right conditions (namely, data-sets that span long durations and contain a high fraction of community-wide collections, or collection events that focus on communities of organisms), models can accurately estimate trends. Finally, we present a case-study on eastern North American odonates where we calculate long-term trends of occupancy by using our most robust workflow.
Inference of Brain States under Anesthesia with Meta Learning Based Deep Learning Models
Authors: Wang Qihang , Liu Feng , Wan Guihong , Chen Ying
Published: December 2021

Monitoring the depth of unconsciousness during anesthesia is useful in both clinical settings and neuroscience investigations to understand brain mechanisms. Electroencephalogram (EEG) has been used as an objective means of characterizing brain altered arousal and/or cognition states induced by anesthetics in real-time. Different general anesthetics affect cerebral electrical activities in different ways. However, the performance of conventional machine learning models on EEG data is unsatisfactory due to the low Signal to Noise Ratio (SNR) in the EEG signals, especially in the office-based anesthesia EEG setting. Deep learning models have been used widely in the field of Brain Computer Interface (BCI) to perform classification and pattern recognition tasks due to their capability of good generalization and handling noises. Compared to other BCI applications, where deep learning has demonstrated encouraging results, the deep learning approach for classifying different brain consciousness states under anesthesia has been much less investigated. In this paper, we propose a new framework based on meta-learning using deep neural networks, named Anes-MetaNet, to classify brain states under anesthetics. The Anes-MetaNet is composed of Convolutional Neural Networks (CNN) to extract power spectrum features, and a time consequence model based on Long Short-Term Memory (LSTM) Networks to capture the temporal dependencies, and a meta-learning framework to handle large cross-subject variability. We used a multi-stage training paradigm to improve the performance, which is justified by visualizing the high-level feature mapping. Experiments on the office-based anesthesia EEG dataset demonstrate the effectiveness of our proposed Anes-MetaNet by comparison of existing methods.
Genome-wide association study across five cohorts identifies five novel loci associated with idiopathic pulmonary fibrosis
Authors: Allen Richard J , Stockwell Amy , Oldham Justin M , Guillen-Guio Beatriz , Flores Carlos , Noth Imre , Yaspan Brian L , Jenkins R Gisli , Wain Louise V ,   International IPF Genetics Consortium
Published: December 2021

Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition with poor survival times. We previously published a genome-wide meta-analysis of IPF risk across three studies with independent replication of associated variants in two additional studies. To maximise power and to generate more accurate effect size estimates, we performed a genome-wide meta-analysis across all five studies included in the previous IPF risk GWAS. We utilised the distribution of effect sizes across the five studies to assess the replicability of the results and identified five robust novel genetic association signals implicating mTOR signalling, telomere maintenance and spindle assembly genes in IPF risk.
A luciferase prosubstrate and a red bioluminescent calcium indicator to image neuronal activity
Authors: Tian Xiaodong , Zhang Yiyu , Li Xinyu , Xiong Ying , Wu Tianchen , Ai Hui-wang
Published: December 2021

Genetically encoded fluorescent indicators have been broadly used to monitor neuronal activity in live animals, but invasive surgical procedures are required. This study presents a functional bioluminescence imaging (fBLI) method for recording the activity of neuronal ensembles in the brain in awake mice. We developed a luciferase prosubstrate activatable in vivo by nonspecific esterase to enhance the brain delivery of the luciferin. We further engineered a bright, bioluminescent indicator with robust responsiveness to calcium ions (Ca2+) and appreciable emission above 600 nm. Integration of these advantageous components enabled the imaging of Ca2+ dynamics in awake mice minimally invasively with excellent signal- to-background and subsecond temporal resolution. This study thus establishes a new paradigm for studying brain functions in health and disease.
Endurance exercise ameliorates phenotypes in Drosophila models of Spinocerebellar Ataxias
Authors: Sujkowski Alyson , Richardson Kristin , Prifti Matthew V. , Wessells R. J. , Todi Sokol V.
Published: December 2021

Endurance exercise is a potent intervention with widespread benefits proven to reduce disease incidence and impact across species. While endurance exercise supports neural plasticity, enhanced memory, and reduced neurodegeneration, less is known about the effect of chronic exercise on the progression of movement disorders such as ataxias. Here, we focused on three different types of ataxias, Spinocerebellar Ataxias Type (SCAs) 2, 3, and 6, belonging to the polyglutamine (polyQ) family of neurodegenerative disorders. In Drosophila models of these SCAs, flies progressively lose motor function. Here, we observe marked protection of speed and endurance in exercised SCA2 flies and modest protection in exercised SCA6 models, while no benefit is observed in SCA3 flies. Causative protein levels are reduced in SCA2 flies after chronic exercise, but not in SCA3 models, linking protein levels to exercise-based benefits. Additional investigations indicate that the exercise-inducible protein, Sestrin (Sesn) suppresses mobility decline and improves early death in SCA2 flies, even without exercise, coincident with disease protein level reduction and increased autophagic flux. These improvements depend on previously established functions of Sesn that reduce oxidative damage and modulate mTOR activity. Our study suggests differential responses of polyQ SCAs to exercise, highlighting the potential for more extensive application of exercise-based therapies in the prevention of polyQ neurodegeneration. Defining the mechanisms by which endurance exercise suppresses polyQ SCAs will open the door for more effective treatment for these diseases.
Oscillatory movement of a dynein-microtubule complex crosslinked with DNA origami
Authors: Abdellatef Shimaa A. , Tadakuma Hisashi , Yan Kangmin , Fujiwara Takashi , Fukumoto Kodai , Kondo Yuichi , Takazaki Hiroko , Boudria Rofia , Yasunaga Takuo , Higuchi Hideo , Hirose Keiko
Published: December 2021

During repetitive bending of cilia and flagella, axonemal dynein molecules move in an oscillatory manner along a microtubule (MT), but how the minus-end-directed motor dynein can oscillate back and forth is unknown. There are various factors that may regulate the dynein activities, e.g., the nexin-dynein regulatory complex, radial spokes, and central apparatus. In order to understand the basic mechanism of the oscillatory movement, we constructed a simple model system composed of MTs, outer-arm dyneins, and DNA origami that crosslinks the MTs. Electron microscopy (EM) showed patches of dynein molecules crossbridging two MTs in two opposite orientations; the oppositely oriented dyneins are expected to produce opposing forces. The optical trapping experiments showed that the dynein-MT-DNA-origami complex actually oscillate back and forth after photolysis of caged ATP. Intriguingly, the complex, when held at one end, showed repetitive bending motions. The results show that a simple system composed of ensembles of oppositely oriented dyneins, MTs, and inter-MT crosslinkers, without the additional regulatory structures, has an intrinsic ability to cause oscillation and repetitive bending motions.
Visualizing cell death in live retina: Using calpain activity detection as a biomarker for retinal degeneration
Authors: Belhadj Soumaya , Hermann Nina , Christensen Gustav , Strasser Torsten , Paquet-Durand François
Published: December 2021

Calpains are a family of calcium-activated proteases involved in numerous disorders. Notably, previous studies have shown that calpain activity was substantially increased in various models for inherited retinal degeneration (RD). In the present study, we tested the capacity of the t-BOC-Leu-Met-CMAC calpain-specific substrate to detect calpain activity in living retina, in organotypic retinal explant cultures derived from wild-type mice, as well as from rd1 and RhoP23H/+ RD-mutant mice. Test conditions were refined until the calpain substrate readily detected large numbers of cells in the photoreceptor layer of RD retina but not in wild-type retina. At the same time, the calpain substrate was not obviously toxic to photoreceptor cells. Comparison of calpain activity with an immunostaining for activated calpain-2 furthermore suggested that individual calpain isoforms may be active in distinct temporal stages of photoreceptor cell death. Notably, calpain-2 activity may be a relatively short-lived event, occurring only towards the end of the cell death process. Finally, our results support the development of calpain activity detection as a novel in vivo biomarker for RD, suitable for combination with non-invasive imaging techniques.
Azotobacter vinelandii scaffold protein NifU transfers iron to NifQ as part of the iron-molybdenum cofactor biosynthesis pathway for nitrogenase
Authors: Barahona Emma , Jiang Xi , Jiménez-Vicente Emilio , Rubio Luis M. , González-Guerrero Manuel
Published: December 2021

Azotobacter vinelandii molybdenum-dependent nitrogenase obtains molybdenum from NifQ, a monomeric iron-sulfur molybdoprotein. This protein requires of a preexisting [Fe-S] cluster to form a [MoFe3S4] group to serve as specific donor during nitrogenase cofactor biosynthesis. Here, we show biochemical evidence for NifU being the donor of the [Fe-S] cluster. Protein-protein interaction studies using apo-NifQ and as-isolated NifU demonstrated the interaction between both proteins which is only effective when NifQ is unoccupied by its [Fe-S] cluster. The apo-NifQ iron content increased after the incubation with as-isolated NifU, reaching similar levels to holo-NifQ after the interaction between apo-NifQ and NifU with reconstituted transient [Fe4-S4] groups. These results also indicate the necessity of co-expressing NifU together with NifQ in the pathway to provide molybdenum for the biosynthesis of nitrogenase in engineered nitrogen-fixing plants.
Dispersal syndrome and landscape fragmentation in the salt-marsh specialist spiderErigone longipalpis
Authors: Dahirel Maxime , Wullschleger Marie , Berry Tristan , Croci Solène , Pétillon Julien
Published: December 2021

Dispersal and its evolution play a key role for population persistence in fragmented landscapes where habitat loss and fragmentation increase the cost of between-habitat movements. In such contexts, it is important to know how variation in dispersal and other traits is structured, and whether responses to landscape fragmentation are aligned with underlying dispersal-trait correlations, or dispersal syndromes. We therefore studied trait variation inErigone longipalpis, a European spider species specialist of (often patchy) salt marshes. We collected spiders in two salt-marsh landscapes differing in habitat availability. We then reared lab-born spiders for two generations in controlled conditions, and measured dispersal and its association with various key traits.E. longipalpispopulation densities were lower in the more fragmented landscape. Despite this, we found no evidence of differences in dispersal, or any other trait we studied, between the two landscapes. While a dispersal syndrome was present at the among-individual level (dispersers were more fecund and faster growing, among others), there was no indication it was genetically driven: among-family differences in dispersal were not correlated with differences in other traits. Instead, we showed that the observed phenotypic covariations were mostly due to within-family correlations. We hypothesize that the dispersal syndrome is the result of asymmetric food access among siblings, leading to variation in development rates and carrying over to adult traits. Our results show we need to better understand the sources of dispersal variation and syndromes, especially when dispersal may evolve rapidly in response to environmental change.
Insertions in the SARS-CoV-2 Spike N-Terminal Domain May Aid COVID-19 Transmission
Authors: Lam Su Datt , Waman Vaishali P , Orengo Christine , Lees Jonathan
Published: December 2021

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an ongoing pandemic that causes significant health/socioeconomic burden. Variants of concern (VOCs) have emerged which may affect transmissibility, disease severity and re-infection risk. Most studies focus on the receptor-binding domain (RBD) of the Spike protein. However, some studies suggest that the Spike N-terminal domain (NTD) may have a role in facilitating virus entry via sialic-acid receptor binding. Furthermore, most VOCs include novel NTD variants. Recent analyses demonstrated that NTD insertions in VOCs tend to lie close to loop regions likely to be involved in binding sialic acids. We extended the structural characterisation of these putative sugar binding pockets and explored whether variants could enhance the binding to sialic acids and therefore to the host membrane, thereby contributing to increased transmissibility. We found that recent NTD insertions in VOCs (i.e., Gamma, Delta and Omicron variants) and emerging variants of interest (VOIs) (i.e., Iota, Lambda, Theta variants) frequently lie close to known and putative sugar-binding pockets. For some variants, including the recent Omicron VOC, we find increases in predicted sialic acid binding energy, compared to the original SARS-CoV-2, which may contribute to increased transmission. We examined the similarity of NTD across a range of related Betacoronaviruses to determine whether the putative sugar-binding pockets are sufficiently similar to be exploited in drug design. Despite global sequence and structure similarity, most sialic-acid binding pockets of NTD vary across related coronaviruses. Typically, SARS-CoV-2 possesses additional loops in these pockets that increase contact with polysaccharides. Our work suggests ongoing evolutionary tuning of the sugar-binding pockets in the virus. Whilst three of the pockets are too structurally variable to be amenable to pan Betacoronavirus drug design, we detected a fourth pocket that is highly structurally conserved and could therefore be investigated in pursuit of a generic drug. Our structure-based analyses help rationalise the effects of VOCs and provide hypotheses for experiments. For example, the Omicron variant, which has increased binding to sialic acids in pocket 3, has a rather unique insertion near pocket 3. Our work suggests a strong need for experimental monitoring of VOC changes in NTD.
Learning Active Multimodal Subspaces in the Brain
Authors: Batta Ishaan , Abrol Anees , Fu Zening , Calhoun Vince D.
Published: December 2021

Here we introduce a multimodal framework to identify subspaces in the human brain that are defined by collective changes in structural and functional measures and are actively linked to demographic, biological and cognitive indicators in a population. We determine the multimodal subspaces using principles of active subspace learning (ASL) and demonstrate its application on a sample learning task (biological ageing) on a Schizophrenia dataset. The proposed multimodal ASL method successfully identifies latent brain representations as subsets of brain regions and connections forming co-varying subspaces in association with biological age. We show that Schizophrenia is characterized by different subspace patterns compared to those in a cognitively normal brain. The multimodal features generated by projecting structural and functional MRI components onto these active subspaces perform better than several PCA-based transformations and equally well when compared to non-transformed features on the studied learning task. In essence, the proposed method successfully learns active brain subspaces associated with a specific brain condition but inferred from the brain imaging data along with the biological/cognitive traits of interest.
Floral evolution and pollinator diversification inHedychiumJ.Koenig (Zingiberaceae): one of Mr. Darwin’s tropical fantasies
Authors: Ashokan Ajith , Suksathan Piyakaset , Leong-Škorničková Jana , Newman Mark , Kress W. John , Gowda Vinita
Published: December 2021

PREMISE

HedychiumJ.Koenig (ginger lilies: Zingiberaceae) is endemic to the Indo-Malayan Realm (IMR) and is known for its fragrant flowers. Two different pollination syndromes characterize the genus: diurnal or bird pollination and nocturnal or moth pollination systems. To date, no attempt has been undertaken to understand the evolution of floral traits in this genus.

METHODS

We estimated ancestral character-states, phylogenetic signals, and character correlations for thirteen discrete and eight continuous floral traits representing 75% species diversity ofHedychium. Diversification rate estimation analyses were also employed to understand trait-dependent diversification in the genus.

RESULTS

Inflorescence structure, cincinnus capacity, and curvature of floral tubes revealed strong phylogenetic dependence, whereas number of open flowers per inflorescence per day, color of the labellum, and exertion of the stigma characterized higher ecological effects. Diversification rate estimations suggested that the labellum width, floral tube length, and labellum color played a major role in the evolutionary diversification ofHedychium.

CONCLUSIONS

We identified bract type and cincinnus capacity as synapomorphies forHedychium, while the island-specific clade III was characterized by slender cylindrical inflorescence, coiling of floral tubes, and longer bract to calyx ratio. The circum-Himalayan clade IV is the most speciose, derived, and with most variable floral traits. Although floral color and size lacked any association with pollinator-specific traits (moth and bird pollination), pale colored flowers were most common in the early diverging clades (clade I, II-el., and II-de.), indicating their ancestral nature, when compared to brightly colored flowers.
Decoupling SARS-CoV-2 ORF6 localization and interferon antagonism
Authors: Wong Hoi Tong , Cheung Victoria , Salamango Daniel J.
Published: December 2021

Like many pathogenic viruses, SARS-CoV-2 must overcome interferon (IFN)-mediated host defenses for infection establishment. To achieve this, SARS-CoV-2 deploys overlapping mechanisms to antagonize IFN production and signaling. The strongest IFN antagonist is the accessory protein ORF6, which localizes to multiple membranous compartments, including the nuclear envelope, where it directly binds the nuclear pore components Nup98-Rae1 to inhibit nuclear translocation of activated STAT1/IRF3 transcription factors. However, a direct cause-and-effect relationship between ORF6 localization and IFN antagonism has yet to be explored experimentally. Here, we use extensive mutagenesis studies to define the structural determinants required for steady-state localization and demonstrate that mis-localized ORF6 variants can still potently inhibit nuclear trafficking and IFN signaling. Additionally, expression of a peptide that mimics the ORF6/Nup98 interaction domain robustly inhibited nuclear trafficking. Furthermore, pharmacologic and mutational approaches combined to suggest that ORF6 is likely a peripheral-membrane protein, opposed to being a transmembrane protein as previously speculated. Thus, ORF6 localization and IFN antagonism are independent activities, which raises the possibility that ORF6 may have additional functions within membrane networks to enhance virus replication.
Escherichia coli antimicrobial resistance; Phenotypic and genotypic characterization
Authors: Elsharawy Nagwa Thabet , Al-Zahrani Hind A. A. , El-Waseif Amr A.
Published: December 2021

Improper use of the antimicrobials as E. coli giving the microorganism multi-resistance against many antimicrobials by gene mutation on integrons, transposons and plasmids. Therefore, our aim in this study is to 1)examine antibiotics resistance phenotype and genotype in Escherichia coli, 2) identifying the structure of bacterial resistance genes on whole-genome sequencing against multi-drug resistant of Escherichia coli in marketed poultry meat. Samples collected, prepared and Bacteriological examination, Antimicrobial sensitivity test performed, Serological identification of Escherichia coli isolates. Results declared that; the prevalence of E. coli from tested chicken meat samples of 100 chicken meat samples surveyed against E. coli the result declared that about 40%. Antimicrobial susceptibility was; antibiotics of choice against E. coli Sulfonamides, Cephalosporins,Tetracyclines, Quinolones. Serologically, STEC (O157:H7) 30%, ETEC (O142) 10%, EHEC (O26:H11). The subunit B of shiga-like toxin (SLT) gene appeared as a homogenous band. Heat-labile toxin (LT) gene was screened in both genomic DNA and plasmid preps in tested strains. Control STEC as it represents a danger to the poultry consumers. We recommended to increase the hygienic measures during slaughtering, processing and/or handling of chicken carcasses and avoidance unnecessary usage of any antimicrobials to avoid appearance of new antimicrobials resistant.
BDNF-dependent modulation of axonal transport is selectively impaired in ALS
Authors: Tosolini Andrew P. , Sleigh James N. , Surana Sunaina , Rhymes Elena R. , Cahalan Stephen D. , Schiavo Giampietro
Published: December 2021

Axonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments of neurons, and is needed for neuronal development, function, and survival. Deficits in axonal transport have been detected at pre-symptomatic stages in mouse models of amyotrophic lateral sclerosis (ALS), suggesting that impairments are fundamental for disease pathogenesis. However, the precise mechanisms responsible for the transport deficits and whether they preferentially affect α-motor neuron (MN) subtypes remain unresolved. Here, we report that stimulation of wild-type neurons with brain-derived neurotrophic factor (BDNF) enhances trafficking of signalling endosomes specifically in fast MNs (FMNs). In early symptomatic SOD1G93Amice, FMNs display selective impairment of axonal transport and develop an insensitivity to BDNF stimulation, with pathology upregulating classical non-pro-survival receptors in muscles and sciatic nerves. Altogether, these data indicate that cell- and non-cell autonomous BDNF signalling is impaired in vulnerable SOD1G93AMNs, thus identifying a new key deficit in ALS amenable for future therapeutic interventions.
Slit-Robo Signalling Establishes a Sphingosine-1-Phosphate Gradient to Polarise Fin Mesenchyme and Establish Fin Morphology
Authors: Mahabaleshwar Harsha , Asharani P.V. , Yi Jun Tricia Loo , Koh Shze Yung , Pitman Melissa R. , Kwok Samuel , Ma Jiajia , Hu Bo , Lin Fang , Li Lok Xue , Pitson Stuart M. , Saunders Timothy E. , Carney Tom J.
Published: December 2021

Immigration of mesenchymal cells into the growing fin and limb buds drives distal outgrowth, with subsequent tensile forces between these cells essential for fin and limb morphogenesis. Morphogens derived from the apical domain of the fin, orientate limb mesenchyme cell polarity, migration, division and adhesion. The zebrafish mutantstompdisplays defects in fin morphogenesis including blister formation and associated loss of orientation and adhesion of immigrating fin mesenchyme cells. Positional cloning ofstompidentified a mutation in the gene encoding the axon guidance ligand, Slit3. We provide evidence that Slit ligands derived from immigrating mesenchyme act via Robo receptors at the Apical Ectodermal Ridge (AER) to promote release of sphingosine-1-phosphate (S1P). S1P subsequently diffuses back to the mesenchyme to promote their polarisation, orientation, positioning and adhesion to the interstitial matrix of the fin fold. We thus demonstrate coordination of the Slit-Robo and S1P signalling pathways in fin fold morphogenesis. Our work introduces a mechanism regulating the orientation, positioning and adhesion of its constituent cells.
Seroprevalence of brucellosis and molecular characterization of Brucella spp. from slaughtered cattle in Rwanda
Authors: Ntivuguruzwa Jean Bosco , Kolo Francis Babaman , Mwikarago Emil Ivan , vanHeerden Henriette
Published: December 2021

Bovine brucellosis is endemic in Rwanda, although, there is paucity of documented evidence about the disease in slaughtered cattle. A cross-sectional study was conducted in slaughtered cattle (n=300) to determine the seroprevalence of anti-Brucella antibodies using the Rose Bengal Test (RBT), and indirect enzyme-linked immunosorbent assay (i-ELISA). Corresponding tissues were cultured onto a modified Centro de Investigación y Tecnología Agroalimentaria (CITA) selective medium and analysed for Brucella spp. using the 16S-23S ribosomal interspacer region (ITS), AMOS, and Bruce-ladder PCR assays. The RBT seroprevalence was 20.7% (62/300), and 2.9% (8/300) with i-ELISA and 2.9% (8/300) using both tests in parallel. Brucella specific 16S-23S ribosomal DNA interspace region (ITS) PCR detected Brucella DNA in 5.6% (17/300; Brucella culture prevalence). AMOS-PCR assay identified mixed B. abortus and B. melitensis (n=3), B. abortus (n=3) and B. melitensis (n=5) while Bruce-ladder PCR also identified B. abortus (n=5) and B. melitensis (n=6). The gold standard culture method combined with PCR confirmation identified 5.6% Brucella cultures which is higher than the more sensitive seroprevalence of 2.9%. This emphasizes the need to validate the serological tests in Rwanda. The mixed infection caused by B. abortus and B. melitensis in slaughtered cattle indicates cross-infection and poses a risk of exposure potential to abattoir workers. It is essential to urgently strengthen the national bovine brucellosis control program through vaccination as well as test- and-slaughter.
RefSeq Functional Elements as experimentally assayed nongenic reference standards and functional interactions in human and mouse
Authors: Farrell Catherine M. , Goldfarb Tamara , Rangwala Sanjida H. , Astashyn Alexander , Ermolaeva Olga D. , Hem Vichet , Katz Kenneth S. , Kodali Vamsi K. , Ludwig Frank , Wallin Craig L. , Pruitt Kim D. , Murphy Terence D.
Published: December 2021

Eukaryotic genomes contain many nongenic elements that function in gene regulation, chromosome organization, recombination, repair, or replication, and mutation of those elements can affect genome function and cause disease. Although numerous epigenomic studies provide high coverage of gene regulatory regions, those data are not usually exposed in traditional genome annotation and can be difficult to access and interpret without field-specific expertise. The National Center for Biotechnology Information (NCBI) therefore provides RefSeq Functional Elements (RefSeqFEs), which represent experimentally validated human and mouse nongenic elements derived from the literature. The curated data set is comprised of richly annotated sequence records, descriptive records in the NCBI Gene database, reference genome feature annotation, and activity-based interactions between nongenic regions, target genes, and each other. The data set provides succinct functional details and transparent experimental evidence, leverages data from multiple experimental sources, is readily accessible and adaptable, and uses a flexible data model. The data have multiple uses for basic functional discovery, bioinformatics studies, genetic variant interpretation; as known positive controls for epigenomic data evaluation; and as reference standards for functional interactions. Comparisons to other gene regulatory data sets show that the RefSeqFE data set includes a wider range of feature types representing more areas of biology, but it is comparatively smaller and subject to data selection biases. RefSeqFEs thus provide an alternative and complementary resource for experimentally assayed functional elements, with future data set growth expected.
A novel hydrogen-bondingN-oxide–sulfonamide–nitro N—H...O synthon determining the architecture of benzenesulfonamide cocrystals
Authors: Wzgarda-Raj Kinga , Rybarczyk-Pirek Agnieszka J. , Wojtulewski Sławomir , Palusiak Marcin
Published: December 2021

The structures of novel cocrystals of 4-nitropyridineN-oxide with benzenesulfonamide derivatives, namely, 4-nitrobenzenesulfonamide–4-nitropyridineN-oxide (1/1), C5H4N2O3·C6H6N2O4S, and 4-chlorobenzenesulfonamide–4-nitropyridineN-oxide (1/1), C6H6ClNO2S·C5H4N2O3, are stabilized by N—H...O hydrogen bonds, with the sulfonamide group acting as a proton donor. The O atoms of theN-oxide and nitro groups are acceptors in these interactions. The latter is a double acceptor of bifurcated hydrogen bonds. Previous studies on similar crystal structures indicated competition between these functional groups in the formation of hydrogen bonds, with the priority being for theN-oxide group. In contrast, the present X-ray studies indicate the existence of a hydrogen-bonding synthon including N—H...O(N-oxide) and N—H...O(nitro) bridges. We present here a more detailed analysis of theN-oxide–sulfonamide–nitro N—H...O ternary complex with quantum theory computations and the Quantum Theory of Atoms in Molecules (QTAIM) approach. Both interactions are present in the crystals, but the O atom of theN-oxide group is found to be a more effective proton acceptor in hydrogen bonds, with an interaction energy about twice that of the nitro-group O atoms.
Crystal structure and Hirshfeld surface analysis of 3-(hydroxymethyl)-3-methyl-2,6-diphenylpiperidin-4-one
Authors: Gümüş Mustafa Kemal , Kansiz Sevgi , Tulemisova Gulzhamal Bagitovna , Dege Necmi , Saif Eiad
Published: December 2021

A new synthesis of the title compound, C19H21NO2, was developed with good yield and purity using the reaction of 4-hydroxy-3-methyl-2-butanone, benzaldehyde and ammonium acetate in glacial acetic acid as a solvent. The central piperidine ring adopts a chair conformation, and its least-squares basal plane forms dihedral angles of 85.71 (11) and 77.27 (11)° with the terminal aromatic rings. In the crystal, the molecules are linked by O—H...O and C—H...O hydrogen bonds into double ribbons. The Hirshfeld surface analysis shows that the most important contributions are from H...H (68%), C...H/H...C (19%) and O...H/H...O (12%) interactions.
Towards an increased understanding of learning: a case study of a collaborative relationship between a retailer and a logistics service provider
Authors: Haag Linnea , Sandberg Erik , Sallnäs Uni
Published: December 2021

Purpose

This study aims to explain how learning occurs in collaborative retailer–logistics service provider (LSP) relationships. The research is guided by two research questions, addressing absorptive and desorptive capacities and the interaction between these capacities.

Design/methodology/approach

The study is based on a case study of a Swedish, collaborative retailer–LSP dyad. The empirical data are structured around five specific learning situations within the retailer–LSP dyad.

Findings

The findings provide an explanation for how learning occurs within a collaborative retailer–LSP relationship based on subprocesses of absorptive and desorptive capacities. The interaction between these processes is found to rely on two types of support: one-directional and bidirectional. The findings also indicate positive outcomes of learning, such as improved cost efficiencies in warehouse operations, better customer services and improved long-term strategic planning.

Practical implications

This study shows how retailers and LSPs can learn from each other and together create an improved logistics system for end customers.

Originality/value

This research takes into account absorptive and desorptive capacities in a collaborative retailer–LSP relationship. This study enhances the understanding of inter-organisational learning processes in a retail logistics context.
Cross-fertilization of knowledge and technologies in collaborative research projects
Authors: González-Piñero Manel , Páez-Avilés Cristina , Juanola-Feliu Esteve , Samitier Josep
Published: December 2021

Purpose

This paper aims to explore how the cross-fertilization of knowledge and technologies in EU-funded research projects, including serious games and gamification, is influenced by the following variables: multidisciplinarity, knowledge base and organizations (number and diversity). The interrelation of actors and projects form a network of innovation. The largest contribution to cross-fertilization comes from the multidisciplinary nature of projects and the previous knowledge and technology of actors. The analysis draws on the understanding of how consortia perform as an innovation network, what their outcomes are and what capabilities are needed to reap value.

Design/methodology/approach

All the research projects including serious games and/or gamification, funded by the EU-Horizon 2020 work programme, have been analyzed to test the hypotheses in this paper. The study sample covers the period between 2014 and 2016 (June), selecting the 87 research projects that comprised 519 organizations as coordinators and participants, and 597 observations – because more organizations participate in more than one project. The data were complemented by documentary and external database analysis.

Findings

To create cross-fertilization of knowledge and technologies, the following emphasis should be placed on projects: partners concern various disciplines; partners have an extensive knowledge base for generating novel combinations and added-value technologies; there is a diverse typology of partners with unique knowledge and skills; and there is a limited number of organizations not too closely connected to provide cross-fertilization.

Research limitations/implications

First, the database sample covers a period of 30 months. The authors’ attention was focused on this period because H2020 prioritized for the first time the serious games and gamification with two specific calls (ICT-21–14 and ICT-24–16) and, second, for the explosion of projects including these technologies in the past years (Adkins, 2017). These facts can be understood as a way to push the research to higher technology readiness levels (TRLs) and introducing the end-user in the co-creation and co-development along the value chain. Second, an additional limitation makes reference to the European focus of the projects, missing strong regional initiatives not identified and studied.

Originality/value

This paper has attempted to explore and define theoretically and empirically the characteristics found in the cross-fertilization of collaborative research projects, emphasizing which variables, and how, need to be stimulated to benefit more multidisciplinary consortia and accelerate the process of innovation.
Turning visions into results: unraveling the distinctive paths of leading with vision and autonomy to goal achievement
Authors: Maran Thomas K. , Baldegger Urs , Klösel Kilian
Published: December 2021

Purpose

Leading with vision while granting employees autonomy is one effective organizational response to the demands of a dynamic external environment. The former is thought to align followers' behavior by providing guidance, the latter to increase variance in their behavior by relinquishing control; both exert beneficial but distinct effects on organizational performance. What has remained uncharted heretofore is how these leader behaviors shape their followers' cognition and, subsequently, yield improvements in performance. The authors argue that a leader's vision communication transforms followers' cognitive representation of their work. This not only enables them to specify their goals in alignment with the vision (goal clarity) but also to locate the meaning of their work within the bigger picture of the vision (construal level). By contrast, perceived autonomy in terms of power-sharing might directly affect followers' work engagement more narrowly.

Design/methodology/approach

The authors tested the model on a sample of 408 employees from eleven enterprises of a holding company. In the survey, employees reported perceived vision communication and autonomy provided by their leader. Furthermore, the authors assessed the employees' goal attainment. To capture how employees represent their daily work activities, the authors measured their construal level and their goal clarity.

Findings

The results show that both perceived vision communication and granted autonomy improve employees' goal achievement. Moreover, two processes mediate the relationship between vision communication and goal achievement in followers: first, specifying goals in terms of clarity; second, composing a higher-level mental construal of their work. In contrast, no mediation of empowering leader behaviors was found.

Originality/value

Better goal achievement through visionary leadership is therefore achieved through cognitive alignment of followers, while leader-granted autonomy acts as a motivational tool directly on performance.
High variation in hydraulic efficiency but not xylem safety between roots and branches in four temperate broad‐leaved tree species
Authors: Lübbe Torben , Lamarque Laurent J. , Delzon Sylvain , Torres Ruiz José M. , Burlett Régis , Leuschner Christoph , Schuldt Bernhard
Published: December 2021

Xylem hydraulic safety and efficiency are key traits determining tree fitness in a warmer and drier world. While numerous plant hydraulic studies have focused on branches, our understanding of root hydraulic functioning remains limited, although roots control water uptake, influence stomatal regulation and have commonly been considered as the most vulnerable organ along the hydraulic pathway.

We investigated 11 traits related to xylem safety and efficiency along the hydraulic pathway in four temperate broad‐leaved tree species.

Continuous vessel tapering from coarse roots to stems and branches caused considerable reduction in hydraulic efficiency. Wood density was always lowest in roots, but did not decline linearly along the flow path. In contrast, xylem embolism resistance (P50) did not differ significantly between roots and branches, except for one species. The limited variation in xylem safety between organs did not adequately reflect the corresponding reductions in vessel diameter (by ~70%) and hydraulic efficiency (by ~85%). Although we did not observe any trade‐off between xylem safety and specific conductivity, vessel diameter, vessel lumen fraction and wood density were related to embolism resistance, both across and partly within organs.

We conclude that coarse roots are not highly vulnerable to xylem embolism as commonly believed, indicating that hydraulic failure during soil drying might be restricted to fine roots.

A free Plain Language Summary can be found within the Supporting Information of this article.
How Do Mutual Dependence and Power Imbalance Condition the Effects of Technological Similarity on Post‐acquisition Innovation Performance Over Time?
Authors: Wu Jie , Yu Luman , Khan Zaheer
Published: December 2021

This study investigates how mutual dependence and power imbalance, which have been differentiated by recent studies adopting the theoretical lens of resource dependence theory (RDT) as two distinct forms of interdependence, change the effect of technological similarity between the acquiring firm and the target firm on post‐acquisition innovation across times. The analysis of panel data on mergers and acquisitions undertaken by US firms reveals that in the short‐run, mutual dependence strengthens the effect of technological similarity on post‐acquisition innovation, whereas power imbalance weakens it. However, the effect of mutual dependence persists over time, while that of power imbalance declines over time. These findings extend the RDT to the context of technological acquisition and innovation and offer important implications for research and practice.
The impossibility of engaged research: Complicity and accountability between researchers, ‘publics’ and institutions
Authors: Heney Veronica , Poleykett Branwyn
Published: December 2021

Over the past decade, U.K. universities have increasingly sought to involve publics in research as active participants in the construction of academic knowledge. Sociologists of health have largely welcomed this enthusiasm for engaged and participatory ways of working, including methodologies long in use in the field such as patient‐led research and co‐creation. Despite the strong interest in engaged research, however, we argue that funding patterns, bureaucratic structures and an overreliance on people employed on casual contracts make it extremely difficult, often impossible, to do engaged research in British universities. Drawing on our own experiences, we show how our attempts to practise and deepen accountability to variously situated publics were constrained by the way our institution imagined and materially supported engagement. We argue that it falls to individual researchers to mitigate or work around structural barriers to engagement, and that this process creates dilemmas of complicity. If engaged research is to fulfil its remit for inclusion and its radical potential, researchers need to think carefully about how the U.K. engagement agenda entwines with processes of casualisation, acceleration and projectification, and how institutional recuperations of engagement can undermine its political and epistemic objectives.
From oasis to outlier: sugar beets, an endangered fish, and the moral economy
Authors: Gewertz Deborah , Errington Frederick
Published: December 2021

Farmers in the arid high plains of Eastern Montana had long irrigated with water shunted into their fields by a dam on the Yellowstone River. Growing water‐hungry sugar beets processed at a factory in a nearby town, they created a verdant and prosperous oasis: a good life nested within a satisfyingly moral economy. However, in short order, the economic basis of this life was challenged: the dam was threatened with removal because of claims that it adversely affected an endangered fish; and the factory was threatened with closure because of claims that it was insufficiently profitable. As farmers and townsfolk confronted these challenges and the motives of those making them, they were compelled to probe the fundamental questions of what is ‘moral’ and what is ‘economy’. Confronting their uncertain future, they wondered whether their oasis was to become an outlier.
Who talks about what? Issue strategies across the party hierarchy
Authors: ENNSER‐JEDENASTIK LAURENZ , HASELMAYER MARTIN , HUBER LENA MARIA , FENZ MARTIN
Published: December 2021

We combine the recent literature on issue competition with work on intra‐party heterogeneity to advance a novel theoretical argument. Starting from the premise that party leaders and non‐leaders have different motivations and incentives, we conjecture that issue strategies should vary across the party hierarchy. We, therefore, expect systematic intra‐party differences in the use ofriding the waveandissue ownershipstrategies. We test this claim by linking public opinion data to manually coded information on over 3600 press releases issued by over 500 party actors across five election campaigns in Austria between 2006 and 2019. We account for self‐selection into leadership roles by exploiting transitions into and out of leadership status over time. The results show that party leaders are more likely than non‐leaders to respond to the public's issue priorities, but not more or less likely to pursue issue‐ownership strategies.
Inhibition of DNA methyltransferase aberrations reinstates antioxidant aging suppressors and ameliorates renal aging
Authors: Gao Qi , Chen Fang , Zhang Lijun , Wei Ai , Wang Yongxiang , Wu Zhiwei , Cao Wangsen
Published: December 2021

DNA methylation alterations play mechanistic roles in aging; however, the epigenetic regulators/mediators causally involved in renal aging remain elusive. Here, we report that natural and D‐galactose (D‐gal)‐induced aging kidneys display marked suppression of antiaging factor NRF2 (nuclear factor erythroid‐derived 2‐like 2) and KLOTHO, accompanied by upregulations of DNA methyltransferase (DNMT) 1/3a/3b and NRF2/KLOTHO gene promoter hypermethylations. Administration of a DNMT inhibitor SGI‐1072 effectively hypomethylated the promoters, derepressed NRF2/KLOTHO, and mitigated the structural and functional alterations of renal aging in D‐gal mice. Moreover, oleuropein (OLP), an olive‐derived polyphenol, also displayed similar epigenetic modulation and antiaging effects. OLP inhibited the epigenetic NRF2/KLOTHO suppressions in a gain of DNMT‐sensitive manner in cultured renal cells, demonstrating a strong DNA‐demethylating capacity. In NRF2 knockout and KLOTHO knockdown D‐gal mice, OLP exhibited reduced antiaging effects with KLOTHO displaying a prominent gene effect and effect size; consistently in KLOTHO knockdown mice, the antiaging effects of SGI‐1027 were largely abrogated. Therefore, the KLOTHO recovery is critical for the antiaging effects of DNA demethylation. Collectively, our data indicate that aberrant DNMT1/3a/3b elevations and the resultant suppression of antiaging factors contribute significantly to epigenetic renal aging, which might be targeted for epigenetic intervention by synthetic or natural DNA‐demethylating agents.