bluuebunny/crossref_metadata_2025 huggingface dataset:
CB1receptor-mediated inhibitory LTD triggers presynaptic remodeling via protein synthesis and ubiquitination
Authors: Monday Hannah R. , Bourdenx Mathieu , Jordan Bryen A. , Castillo Pablo E.
Published: January 2020

Long-lasting forms of postsynaptic plasticity commonly involve protein synthesis-dependent structural changes of dendritic spines. However, the relationship between protein synthesis and presynaptic structural plasticity remains unclear. Here, we investigated structural changes in cannabinoid-receptor 1 (CB1)-mediated long-term depression of inhibitory transmission (iLTD), a form of presynaptic plasticity that requires protein synthesis and involves a long-lasting reduction in GABA release. We found that CB1-iLTD in acute rat hippocampal slices was associated with protein synthesis-dependent presynaptic structural changes. Using proteomics, we determined that CB1activation in hippocampal neurons resulted in increased ribosomal proteins and initiation factors, but decreased levels of proteins involved in regulation of the actin cytoskeleton, such as Arp2/3, and presynaptic release. Moreover, while CB1-iLTD increased ubiquitin/proteasome activity, ubiquitination but not proteasomal degradation was critical for structural and functional presynaptic CB1-iLTD. Thus, CB1-iLTD relies on both protein synthesis and ubiquitination to elicit structural changes that underlie long-term reduction of GABA release.
EEG correlates of physical effort and reward processing during reinforcement learning
Authors: Palidis Dimitrios J. , Gribble Paul L.
Published: January 2020

Effort-based decision making is often described by choices according to subjective value, a function of reward discounted by effort. We asked whether a neural reinforcement learning signal, the feedback related negativity (FRN), is modulated not only by reward outcomes but also physical effort. We recorded EEG from human participants while they performed a task in which they were required to accurately produce target levels of muscle activation to receive rewards. Participants performed isometric knee extensions while quadriceps muscle activation was recorded using EMG. Real-time feedback indicated muscle activation relative to a target. On a given trial, the target muscle activation required either low or high effort. The effort was determined probabilistically according to a binary choice, such that the responses were associated with 20% and 80% probability of high effort. This contingency could only be known by experience, and it reversed periodically. After each trial binary reinforcement feedback was provided to indicate whether participants were sufficiently accurate in producing the target muscle activity. Participants adaptively avoided effort by switching responses more frequently after choices that resulted in hard effort. Feedback after participants’ choices which revealed the resulting effort requirement for the subsequent knee extension did not elicit an FRN component. However, the neural response to reinforcement feedback after the knee extension was increased during and after the time period of the FRN by preceding physical effort. Thus, retrospective effort modulates reward processing which may underlie paradoxical behavioral findings whereby rewards requiring more effort to obtain can become more powerful reinforcers.

Significance Statement

When making decisions, we typically select more rewarding and less effortful options. Neural reinforcement learning signals reinforce rewarding actions and deter punishing actions. When participants received feedback that their choices would require easy or hard physical effort, we did not observe reinforcement learning signals that are typically observed in response to feedback predicting reward and punishment. Thus, the reinforcement learning system does not strictly treat effort as loss or punishment. However, when the effort was completed and participants received feedback indicating whether they successfully achieved a reward or not, reinforcement learning signals were amplified by preceding effort. Thus, retrospective effort can affect neural responses to reinforcement outcomes, which may explain how effort can enhance the motivational effect of reinforcers.
Circadian Rhythm Is Disrupted by ZNF704 in Breast Carcinogenesis
Authors: Yang Chao , Wu Jiajing , Liu Xinhua , Wang Yue , Liu Beibei , Chen Xing , Wu Xiaodi , Yan Dong , Han Lulu , Liu Shumeng , Shan Lin , Shang Yongfeng
Published: January 2020

Copy number gain in chromosome 8q21 is considered as the prototype of genetic abnormalities associated with development of breast cancer, yet the oncogenic potential underlying this amplicon in breast carcinogenesis remains to be delineated. We report here thatZNF704, a gene mapped to 8q21, is recurrently amplified in various malignancies including breast cancer. We found that ZNF704 acts as transcription repressor and interacts with the transcription corepressor SIN3A complex. Genome-wide interrogation of the transcriptional targets identifies that the ZNF704/SIN3A complex represses a panel of genes includingPER2that are critically involved in the function of circadian clock. Indeed, ZNF704 overexpression prolongs the period and dampens the amplitude of circadian clock. We showed that ZNF704 promotes the proliferation and invasion of breast cancer cellsin vitroand accelerates the growth and metastasis of breast cancerin vivo. Consistently, the level of ZNF704 expression is inversely correlated with that of PER2 in breast carcinomas, and high level of ZNF704 correlates with advanced histological grades, lymph node positivity, and poor prognosis of breast cancer patients, especially those with HER2+and basal-like subtypes. These results indicate that ZNF704 is an important regulator of circadian clock and a potential driver for breast carcinogenesis.
A semi-empirical model of the aerodynamics of manoeuvring insect flight
Authors: Walker Simon M. , Taylor Graham K.
Published: January 2020

Blade element modelling provides a quick analytical method for estimating the aerodynamic forces produced during insect flight, but such models have yet to be tested rigorously using kinematic data recorded from free-flying insects. This is largely because of the paucity of detailed free-flight kinematic data, but also because analytical limitations in existing blade element models mean that they cannot incorporate the complex three-dimensional movements of the wings and body that occur during insect flight. Here, we present a blade element model with empirically-fitted aerodynamic force coefficients that incorporates the full three-dimensional wing kinematics of manoeuvringEristalishoverflies, including torsional deformation of their wings. The two free parameters were fitted to a large free-flight dataset comprisingN= 26, 541 wingbeats, and the fitted model captured approximately 80% of the variation in the stroke-averaged forces in the sagittal plane. We tested the robustness of the model by subsampling the data, and found little variation in the parameter estimates across subsamples comprising 10% of the flight sequences. The simplicity and generality of the model that we present is such that it can be readily applied to kinematic datasets from other insects, and also used for the study of insect flight dynamics.
Evolution of contribution timing in public goods games
Authors: Morsky Bryce , Smolla Marco , Akçay Erol
Published: January 2020

Life history strategies are a crucial aspect of life, which are complicated in group-living species, where payoffs additionally depend on others’ behaviours. Previous theoretical models of public good games have generally focused on the amounts individuals contribute to the public good. Yet a much less studied strategic aspect of public good games, the timing of contributions, can also have dramatic consequences for individual and collective performance. Here, we develop game theoretical models to explore how the timing of contributions evolves. We show how contributing rapidly is not necessarily optimal, since delayers can act as “cheats,” avoiding contributing while reaping the benefits of the public good. However, delaying too long can put the delayers at a disadvantage as they can miss out on the benefits. These effects lead to bistability in a single group, and spatial diversity among multiple interacting groups.
Potent inhibitors of toxic alpha-synuclein oligomers identified via cellular time-resolved FRET biosensor
Authors: Braun Anthony R. , Liao Elly E. , Horvath Mian , Young Malaney C. , Lo Chih Hung , Brown Roland , Evans Michael D. , Luk Kelvin , Thomas David D. , Sachs Jonathan N.
Published: January 2020

Preventing or reversing the pathological misfolding and self-association of alpha-synuclein (aSyn) can rescue a broad spectrum of pathological cellular insults that manifest in Parkinson’s Disease (PD), Dementia with Lewy bodies (DLB), and other alpha-synucleinopathies. We have developed a high-throughput, FRET-based drug discovery platform that combines high-resolution protein structural detection in living cells with an array of functional and biophysical assays to identify novel lead compounds that protect SH-SY5Y cells from aSyn induced cytotoxicity as well as inhibiting seeded aSyn aggregation, even at nanomolar concentrations.

Our combination of cellular and cell-free assays allow us to distinguish between direct aSyn binding or indirect mechanisms of action (MOA). We focus on targeting oligomers with the requisite sensitivity to detect subtle protein structural changes that may lead to effective therapeutic discoveries for PD, DLB, and other alpha-synucleinopathies. Pilot high-throughput screens (HTS) using our aSyn cellular FRET biosensors has led to the discovery of the first nanomolar-affinity small molecules that disrupt toxic aSyn oligomers in cells and inhibit cell death. Primary neuron assays of aSyn pathology (e.g. phosphorylation of mouse aSyn PFF) show rescue of pathology for two of our tested compounds. Subsequent seeded thioflavin-t (ThioT) aSyn aggregation assays demonstrate these compounds deter or block aSyn fibril assembly. Other hit compounds identified in our HTS are known to modulate oxidative stress, autophagy, and ER stress, providing validation that our biosensor is sensitive to indirect MOA as well.
Common and distinct brain activity associated with risky and ambiguous decision-making
Authors: Poudel Ranjita , Riedel Michael C. , Salo Taylor , Flannery Jessica S. , Hill-Bowen Lauren D. , Eickhoff Simon B. , Laird Angela R. , Sutherland Matthew T.
Published: January 2020

Two often-studied forms of uncertain decision-making (DM) are risky-DM (outcome probabilities known) and ambiguous-DM (outcome probabilities unknown). While DM in general is associated with activation of several brain regions, previous neuroimaging efforts suggest a dissociation between activity linked with risky and ambiguous choices. However, the common and distinct neurobiological correlates associated with risky- and ambiguous-DM, as well as their specificity when compared to perceptual-DM (as a ‘control condition’), remains to be clarified. We conducted multiple meta-analyses on neuroimaging results from 151 studies to characterize common and domain-specific brain activity during risky-, ambiguous-, and perceptual-DM. When considering all DM tasks, convergent activity was observed in brain regions considered to be consituents of the canonical salience, valuation, and executive control networks. When considering subgroups of studies, risky-DM (vs. perceptual-DM) was linked with convergent activity in the striatum and anterior cingulate cortex (ACC), regions associated with reward-related processes (determined by objective functional decoding). When considering ambiguous-DM (vs. perceptual-DM), activity convergence was observed in the lateral prefrontal cortex and insula, regions implicated in affectively-neutral mental processes (e.g., cognitive control and behavioral responding; determined by functional decoding). An exploratory meta-analysis comparing brain activity between substance users and non-users during risky-DM identified reduced convergent activity among users in the striatum, cingulate, and thalamus. Taken together, these findings suggest a dissociation of brain regions linked with risky- and ambiguous-DM reflecting possible differential functionality and highlight brain alterations potentially contributing to poor decision-making in the context of substance use disorders.
Differences in memory for what, where, and when components of recently-formed episodes
Authors: Sakon John J. , Kiani Roozbeh
Published: January 2020

An integral feature of human memory is the ability to recall past events. What distinguishes such episodic memory from associative and semantic memories is the joint encoding and retrieval of “what,” “where,” and “when” (WWW) of events. Here, we investigated whether the WWW components of episodes are retrieved with equal fidelity. Using a novel task where human participants were probed on the WWW components of a recently-viewed synthetic movie, we found fundamental differences in mnemonic accuracy between these components. The memory of “when” had the lowest accuracy and was most severely influenced by primacy and recency. Further, the memory of “when” and “where” were most susceptible to interference due to changes in memory load. These findings suggest that episodes are not stored and retrieved as a coherent whole. Rather, memory components preserve a degree of independence, suggesting that remembering coherent episodes is an active reconstruction process.
The electrically conductive pili ofGeobacter soli
Authors: Zhuo Shiyan , Yang Guiqin , Zhuang Li
Published: January 2020

Electrically conductive pili (e-pili) enable electron transport over multiple cell lengths to extracellular environments and play an important role in extracellular electron transfer (EET) ofGeobacterspecies. To date, the studies of e-pili have mainly focused onGeobacter sulfurreducensand the closely relatedGeobacter metallireducensbecause of their developed genetic manipulation systems. We investigated the role ofG. solipili in EET by directly deleting the pilin gene,pilA, which is predicted to encode e-pili. Deletion ofpilA, prevented the production of pili, resulting in poor Fe(III) oxide reduction and low current production, implying thatG. solipili is required for EET. To further evaluate the conductivity ofG. solipili compared withG. sulfurreducenspili, thepilAofG. soliwas heterologously expressed inG. sulfurreducens, yielding theG. sulfurreducensstrain GSP. This strain produced abundant pili with similar conductivity to the control strain that expressed nativeG. sulfurreducenspili, consistent withG. solias determined by direct measurement, which suggested thatG. solipili is electrically conductive. Surprisingly, strain GSP was deficient in Fe(III) oxide reduction and current production due to the impaired content of outer-surfacec-type cytochromes. These results demonstrated that heterologous pili ofG. sulfurreducensseverely reduces the content of outer-surfacec-type cytochromes and consequently eliminates the capacity for EET, which strongly suggests an attention should be paid to the content ofc-type cytochromes when employingG. sulfurreducensto heterologously express pili from other microorganisms.

IMPORTANCE

The studies of electrically conductive pili (e-pili) ofGeobacterspecies are of interest because of its application prospects in electronic materials. e-Pili are considered a substitution for electronic materials due to its renewability, biodegradability and robustness. Continued exploration of additional e-pili ofGeobacter soliwill improve the understanding of their biological role in extracellular electron transfer and expand the range of available electronic materials. Heterologously expressing the pilin genes from phylogenetically diverse microorganisms has been proposed as an emerging approach to screen potential e-pili according to high current densities. However, our results indicated that aGeobacter sulfurreducensstrain heterologously expressing a pilin gene produced low current densities that resulted from a lack of content ofc-type cytochromes, which were likely to possess e-pili. These results provide referential significance to yield e-pili from diverse microorganisms.
Comprehensive benchmarking of computational deconvolution of transcriptomics data
Authors: Cobos Francisco Avila , Alquicira-Hernandez José , Powell Joseph , Mestdagh Pieter , De Preter Katleen
Published: January 2020

Many computational methods to infer cell type proportions from bulk transcriptomics data have been developed. Attempts comparing these methods revealed that the choice of reference marker signatures is far more important than the method itself. However, a thorough evaluation of the combined impact of data transformation, pre-processing, marker selection, cell type composition and choice of methodology on the results is still lacking.

Using different single-cell RNA-sequencing (scRNA-seq) datasets, we generated hundreds of pseudo-bulk mixtures to evaluate the combined impact of these factors on the deconvolution results. Along with methods to perform deconvolution of bulk RNA-seq data we also included five methods specifically designed to infer the cell type composition of bulk data using scRNA-seq data as reference.

Both bulk and single-cell deconvolution methods perform best when applied to data in linear scale and the choice of normalization can have a dramatic impact on the performance of some, but not all methods. Overall, single-cell methods have comparable performance to the best performing bulk methods and bulk methods based on semi-supervised approaches showed higher error and lower correlation values between the computed and the expected proportions. Moreover, failure to include cell types in the reference that are present in a mixture always led to substantially worse results, regardless of any of the previous choices. Taken together, we provide a thorough evaluation of the combined impact of the different factors affecting the computational deconvolution task across different datasets and propose general guidelines to maximize its performance.
ARID2deficiency promotes tumor progression and is associated with higher sensitivity to PARP inhibition in lung cancer
Authors: Moreno Thaidy , González-Silva Laura , Monterde Beatriz , Betancor-Fernández Isabel , Revilla Carlos , Agraz-Doblas Antonio , Freire Javier , Isidro Pablo , Quevedo Laura , Montes-Moreno Santiago , Cereceda Laura , Astudillo Aurora , Casar Berta , Crespo Piero , Torres Cristina Morales , Scaffidi Paola , Gomez-Roman Javier , Salido Eduardo , Varela Ignacio
Published: January 2020

The survival rate in lung cancer remains stubbornly low and there is an urgent need for the identification of new therapeutic targets. Last decade’s research has evidenced a clear role of chromatin structure in cancer development and several members of the SWI/SNF chromatin remodeling complexes have been described altered in different tumor types. Nevertheless, the precise mechanisms of their impact on cancer progression, as well as the application of this knowledge to cancer patient management are largely unknown.

In this study, we have performed targeted sequencing of a cohort of lung cancer patients on genes involved in chromatin structure, as well as functional experiments to identify the molecular mechanisms linking alterations of chromatin remodeling genes and tumor development.

We have identified ARID2 production loss in 20% of lung cancer patients. Additionally, we have shown that ARID2-deficiency provokes profound chromatin structural changes, alters the transcriptional programme and impairs DNA repair which bolster the proliferative and metastatic potential of the cells bothin vitroandin vivo. Moreover, we have demonstrated that ARID2 deficiency significantly affects the sensitivity of the cells to PARP inhibition.

All these results support thatARID2is abona-fidetumor suppressor gene in lung cancer that might be exploited therapeutically.
Ocean currents promote rare species diversity in protists
Authors: Martín Paula Villa , Bucek Ales , Bourguignon Tom , Pigolotti Simone
Published: January 2020

Oceans host communities of plankton composed of relatively few abundant species and many rare species. The number of rare protists species in these communities, as estimated in metagenomic studies, decays as a steep power law of their abundance. The ecological factors at the origin of this pattern remain elusive. We propose that oceanic currents affect biodiversity patterns of rare species. To test this hypothesis, we introduce a spatially-explicit coalescence model able to reconstruct the species diversity in a sample of water. Our model predicts, in the presence of oceanic currents, a steeper power law decay of the species abundance distribution and a steeper increase of the number of observed species with sample size. A comparison of two metagenomic studies of planktonic protist communities in oceans and in lakes quantitatively confirms our prediction. Our results support that oceanic currents positively impact the diversity of rare aquatic microbes.
Amino-alcohol Bio-conjugate of Naproxen Exhibits Anti-inflammatory Activity through NF-κB Signaling Pathway
Authors: Das Mahua Rani , Banerjee Anindyajit , Sarkar Sourav , Majumder Joydeb , Chakrabarti Saikat , Jana Siddhartha Sankar
Published: January 2020

Naproxen sodium (Ns) is a well-known synthetic compound used vastly as a nonsteroidal anti-inflammatory drug (NSAID). Previously, we demonstrated that the hydrogels, made of Ns bio-conjugate (NBC), either with amino alcohol (NBC-1 and 2) or amino acid (NBC-3 and 4), displayed anti-inflammatory properties better than Ns, but the effectiveness was not well explored. Here, we investigated that NBC-2, conjugated with γ-amino alcohol, significantly reduces the expression of pro-inflammatory proteins; such as inducible nitric oxide synthase (iNOS) and cyclooxygenase isoform-2 (COX-2), and the production of pro-inflammatory mediator nitric oxide (NO) in lipopolysaccharide and interferon-γ (LPS/IFN-γ) treated mouse macrophage RAW 264.7 cells, compared with bio-conjugation of β-amino alcohol (NBC-1) or β-amino acid (NBC-3) or α-amino acid NBC (NBC-4). NBC-2 decreases the nuclear localization of transcription factors NF-κB by stabilizing its cytoplasmic functional inhibitor IκBα. Moreover, NBC-2 also displays selective inhibitory effect towards COX-1 enzyme activity as determined by enzymatic assay andin silicomolecular docking analysis. Thus, we suggest that NBC-2 may be used as a self-delivery anti-inflammatory drug as compared with other NBCs.

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Gene size matters: What determines gene length in the human genome?
Authors: Lopes Inês , Altab Gulam , Raina Priyanka , de Magalhães João Pedro
Published: January 2020

While it is expected for gene length to be influenced by factors such as intron number and evolutionary conservation, we have yet to fully understand the connection between gene length and function in the human genome.

In this study, we show that, as expected, there is a strong positive correlation between gene length and the number of SNPs, introns and protein size. Amongst tissue specific genes, we find that the longest genes are expressed in blood vessels, nerve, thyroid, cervix uteri and brain, while the smallest genes are expressed within the pancreas, skin, stomach, vagina and testis. We report, as shown previously, that natural selection suppresses changes for genes with longer lengths and promotes changes for smaller genes. We also observed that longer genes have a significantly higher number of co-expressed genes and protein-protein interactions. In the functional analysis, we show that bigger genes are often associated with neuronal development, while smaller genes tend to play roles in skin development and in the immune system. Furthermore, pathways related to cancer, neurons and heart diseases tend to have longer genes, with smaller genes being present in pathways related to immune response and neurodegenerative diseases.

We hypothesise that longer genes tend to be associated with functions that are important early in life, while smaller genes play a role in functions that are important throughout the organisms’ whole life, like the immune system which require fast responses.

Author Summary

Even though the human genome has been fully sequenced, we still do not fully grasp all of its nuances. One such nuance is the length of the genes themselves. Why are certain genes longer than others? Is there a common function shared by longer/smaller genes? What exactly makes gene longer? We tried answering these questions using a variety of analysis. We found that, while there was not a particular strong factor in genes that influenced their size, there could be an influence of several gene characteristics in determining the length of a gene. We also found that longer genes are linked with the development of neurons, cancer, heart diseases and muscle cells, while smaller genes seem to be mostly related with the immune system and the development of the skin. This led us to believe that, whether the gene has an important function early in our life, or throughout our whole lives, or even if the function requires a rapid response, that its gene size will be influenced accordingly.
Extensive nuclear gyration and pervasive non-genic transcription during primordial germ cell development in zebrafish
Authors: Redl Stefan , de Jesus Domingues Antonio M. , Möckel Stefanie , Salvenmoser Willi , Mendez-Lago Maria , Ketting René F.
Published: January 2020

Primordial germ cells (PGCs) are the precursors of germ cells, which migrate to the genital ridge during early development. Relatively little is known about PGCs after their migration. We studied this post-migratory stage using microscopy and sequencing techniques, and found that many PGC-specific genes, including genes known to induce PGC fate in the mouse, are only activated several days after migration. At this same timepoint, PGC nuclei become extremely gyrated, displaying general opening of chromatin and high levels of transcription. This is accompanied by changes in nuage morphology, expression of large loci, named PERLs, enriched for retro-transposons and piRNAs, and a rise in piRNA biogenesis signatures. Interestingly, no nuclear Piwi protein could be detected at any timepoint, indicating that the zebrafish piRNA pathway is fully cytoplasmic. Our data show that the post-migratory stage of zebrafish PGCs holds many cues to both germ cell fate establishment and piRNA pathway activation.
Longitudinal whole-exome sequencing of cell-free DNA unravels the metastatic evolutionary dynamics of BRCA2-mutated breast cancer
Authors: Hastings R.K , Openshaw M.R , Vazquez M , Moreno-Cardenas AB , Fernandez-Garcia D , Martinson L , Toghill B , Kulbicki K , Primrose L , Guttery D.S , Page K , Richards C , Thomas A , Tabernero J , Coombes R.C , Ahmed S , Toledo R.A , Shaw J.A
Published: January 2020

Little is known about the metastatic evolutionary dynamics of BRCA2-mutated cancers. Here, we applied whole-exome sequencing (WES) of primary tumor (PT), local relapse (LR) and eight serial plasma cfDNA samples collected from disease progression to depict the 12 years evolutionary trajectory of a metastatic BRCA2-mutated breast cancer. While longitudinal WES-cfDNA recapitulated clonal and subclonal mutations and copy number profiles detected in LR, emergence of plasma-exclusive mutations in TSC2 and HDAC9 cancer-related genes and loss of HLA loci as an immune escape mechanism were also detected. Lastly, mutation signature 3, associated with homologous recombination deficiency and response to platinum-based therapy raised profoundly from 19% in PT to 60% in late stage disease. In conclusion, we show for the first time that longitudinal WES-cfDNA enables the evolutionary trajectory of advanced cancer to be uncovered and that increment of MS3 and loss of HLA are key players in this BRCA2-mutated breast metastasis.
The Escherichia coli RnlA–RnlB toxin–antitoxin complex: production, characterization and crystallization
Authors: Garcia-Rodriguez Gabriela , Talavera Perez Ariel , Konijnenberg Albert , Sobott Frank , Michiels Jan , Loris Remy
Published: January 2020

The Escherichia coli rnlAB operon encodes a toxin–antitoxin module that is involved in protection against infection by bacteriophage T4. The full-length RnlA–RnlB toxin–antitoxin complex as well as the toxin RnlA were purified to homogeneity and crystallized. When the affinity tag is placed on RnlA, RnlB is largely lost during purification and the resulting crystals exclusively comprise RnlA. A homogeneous preparation of RnlA–RnlB containing stoichiometric amounts of both proteins could only be obtained using a His tag placed C-terminal to RnlB. Native mass spectrometry and SAXS indicate a 1:1 stoichiometry for this RnlA–RnlB complex. Crystals of the RnlA–RnlB complex belonged to space group C2, with unit-cell parameters a = 243.32, b = 133.58, c = 55.64 Å, β = 95.11°, and diffracted to 2.6 Å resolution. The presence of both proteins in the crystals was confirmed and the asymmetric unit is likely to contain a heterotetramer with RnlA2:RnlB2 stoichiometry.
Cocktailed fragment screening by X-ray crystallography of the antibacterial target undecaprenyl pyrophosphate synthase from Acinetobacter baumannii
Authors: Thorpe James H. , Wall Ian D. , Sinnamon Robert H. , Taylor Amy N. , Stavenger Robert A.
Published: January 2020

Direct soaking of protein crystals with small-molecule fragments grouped into complementary clusters is a useful technique when assessing the potential of a new crystal system to support structure-guided drug discovery. It provides a robustness check prior to any extensive crystal screening, a double check for assay binding cutoffs and structural data for binding pockets that may or may not be picked out in assay measurements. The structural output from this technique for three novel fragment molecules identified to bind to the antibacterial target Acinetobacter baumannii undecaprenyl pyrophosphate synthase are reported, and the different physicochemical requirements of a successful antibiotic are compared with traditional medicines.
On the real combinations of cubes and octahedra
Authors: Voytekhovsky Yury L. , Stepenshchikov Dmitry G.
Published: January 2020

All the real combinations of cubes and octahedra (77657 in total) are enumerated and characterized by facet symbols and symmetry point groups. The most symmetrical polyhedra (with automorphism group orders not less than 6, 163 in total) are shown. It is assumed that they represent the most probable forms of natural diamond crystals. The results are discussed with respect to the Curie dissymmetry principle.
Crystal structure and Hirshfeld surface analysis of 1,2,4-triazolium hydrogen oxalate
Authors: Ponjan Nutcha , Aroonchat Purita , Chainok Kittipong
Published: January 2020

The asymmetric unit of the title 1:1 salt 1,2,4-triazolium hydrogen oxalate, C2H4N3
+·C2HO4
− (I), comprises one 1,2,4-triazolium cation and one hydrogen oxalate anion. In the crystal, the hydrogen oxalate anions are linked by O—H...O hydrogen bonds into chains running parallel to [100]. In turn, the anionic chains are linked through the 1,2,4-triazolium cations by charge-assisted +N—H...O− hydrogen bonds into sheets aligned parallel to (01\overline{1}). The sheets are further stacked through π–π interactions between the 1,2,4-triazolium rings [centroid-to-centroid distance = 3.642 (3) Å, normal distance = 3.225 (3) Å, slippage 1.691 Å], resulting in the formation of a three-dimensional supramolecular network. Hirshfeld surface analysis of the title salt suggests that the most significant contributions to the crystal packing are by H...O/O...H and H...N/N...H contacts involving the hydrogen bonds.
3,3-Bis(2-hydroxyethyl)-1-(4-nitrobenzoyl)thiourea: crystal structure, Hirshfeld surface analysis and computational study
Authors: Tan Sang Loon , Jotani Mukesh M. , Tiekink Edward R. T.
Published: January 2020

In the title compound, C12H15N3O5S, a trisubstituted thiourea derivative, the central CN2S chromophore is almost planar (r.m.s. deviation = 0.018 Å) and the pendant hydroxyethyl groups lie to either side of this plane. While to a first approximation the thione-S and carbonyl-O atoms lie to the same side of the molecule, the S—C—N—C torsion angle of −47.8 (2)° indicates a considerable twist. As one of the hydroxyethyl groups is orientated towards the thioamide residue, an intramolecular N—H...O hydrogen bond is formed which leads to an S(7) loop. A further twist in the molecule is indicated by the dihedral angle of 65.87 (7)° between the planes through the CN2S chromophore and the 4-nitrobenzene ring. There is a close match between the experimental and gas-phase, geometry-optimized (DFT) molecular structures. In the crystal, O—H...O and O—H...S hydrogen bonds give rise to supramolecular layers propagating in the ab plane. The connections between layers to consolidate the three-dimensional architecture are of the type C—H...O, C—H...S and nitro-O...π. The nature of the supramolecular association has been further analysed by a study of the calculated Hirshfeld surfaces, non-covalent interaction plots and computational chemistry, all of which point to the significant influence and energy of stabilization provided by the conventional hydrogen bonds.
Crystal structure of the deuterated heptahydrate of potassium phosphate, K3PO4·7D2O
Authors: Weil Matthias , Stöger Berthold
Published: January 2020

Deuterated potassium orthophosphate heptahydrate, K3PO4·7D2O, crystallizes in the Sohnke space groupP21, and its absolute structure was determined from 2017 Friedel pairs [Flack parameter 0.004 (16)]. Each of the three crystallographically unique K+cations is surrounded by six water molecules and one oxygen atom from the orthophosphate group, using a threshold for K—O bonds of 3.10 Å. The highly irregular coordination polyhedra are linked by corner- and edge-sharing into a three-dimensional network that is consolidated by an intricate network of O—D...O hydrogen bonds of medium strength.
The gratifications in the experience of the use of social media and its impact on the purchase and repurchase of products and services
Authors: Santos Corrada Maria , Flecha Jose A. , Lopez Evelyn
Published: January 2020

Purpose

The purpose of this paper is to examine the use of social media and its impact on information search, communication with a company, and purchase and re-purchases of products and services. Using use and gratification theory as a starting point, it also examines the impact of satisfaction of use of social media in the process of purchasing and re-purchasing products and services.

Design/methodology/approach

An online survey was conducted with 444 participants, and the data were analyzed using the partial least squares structural equation modeling technique to observe the effects between the variables of social media use, search information, communication with the company, purchase, re-purchase and satisfaction of use of social media.

Findings

The results reflect how the use of social media generates significant rewards that significantly impact the search for information and the communication with the company. The data also show how communication with the company has an impact on the purchase and re-purchase of products and services. Finally, it was empirically confirmed that the gratification received by users through social media use impacts satisfaction with social media use.

Originality/value

The results contribute to how social media impacts alternative evaluations through the gratification of user needs, resulting in motives and behaviors leading to the purchase of goods and services, as established by Use and Gratification Theory. In its contributions to the Academy, Use and Gratification Theory (U&G) explains why individuals use and share information using social media. First, it justifies the purchase and re-purchase of products and services due to user satisfaction according to users’ experience using social media. Second, it presents a vision of how the use of social media is a significantly important result in the gratification of consumer needs.
A dynamic approach to brand portfolio audit and brand architecture strategy
Authors: Brandão Amélia , Sousa Jose Carlos C. , Rodrigues Clarinda
Published: January 2020

Purpose

This paper aims to propose a dynamic and holistic framework that combines the brand portfolio audit with the brand architecture redesign.

Design/methodology/approach

Depicting from an extensive review on the frameworks of brand audit and brand architecture, a dynamic approach to brand portfolio audit and brand architecture strategy was developed, and later applied and tested in three B2B and B2C companies.

Findings

The paper suggests an eight-step framework to guide practitioners when auditing a specific brand portfolio and designing a revised brand architecture strategy. Additionally, a Brand Audit Scorecard was developed to enable and sustain brand portfolio audits, divided into three dimensions (brand equity, brand contribution and strategic options).

Research limitations/implications

Further research should aim at testing the proposed framework in different types of companies and countries.

Originality/value

This paper contributes to the brand audit and brand architecture literature by proposing a holistic framework that is not static.
Organizational antecedents of exploration and exploitation in SMEs
Authors: Berard Celine , Fréchet Marc
Published: January 2020

Purpose

Scholars have recognized that formal hierarchical structures and slack resources are at the core of small- and medium-sized enterprises (SMEs) attainment of ambidexterity. Surprisingly, few studies on SMEs have analyzed the extent to which these structural and resource attributes are associated with exploration and exploitation. This study aims to examine how two structural attributes, formalization and structural empowerment, and two resource attributes, financial slack and human resource slack, affect exploration and exploitation in SMEs.

Design/methodology/approach

Data were gathered from a survey administered to the chief executive officers of 522 French SMEs. The research hypotheses were then tested using seemingly unrelated regressions to investigate the contrasts between the two components of ambidexterity.

Findings

The results show that structural empowerment and financial slack may be conducive to exploration and exploitation at the same time. By contrast, formalization and human resource slack impact only one of these two ambidexterity components in significant ways: the former may be a powerful lever for exploitation, while the latter may be a powerful lever for exploration.

Originality/value

Relying on a dual structure–resource perspective, this study allows us to discuss the distinct impacts that several organizational antecedents have on exploration and exploitation in the specific context of SMEs. It thus addresses the recent call to identify which antecedents are integrating and which are differentiating to help firms deal with ambidexterity.
Numerical investigation into the stability of earth dam slopes considering the effects of cavities
Authors: Alateya Hawraa , Ahangar Asr Alireza
Published: January 2020

Purpose

This study is an attempt to estimate the influence of the presence of cavities on the stability of slopes in earth dams under rapid drawdown conditions. The purpose of this paper is to study the influence of different factors, such as the diameter and location of cavities, in addition to their existence effects.

Design/methodology/approach

A series of finite element simulation models were developed using PLAXIS 2D finite element software to analyse the stability of slopes in earth dams while considering various effects from cavities in the subsoil under rapid drawdown conditions.

Findings

The results indicated that the presence of cavities and an increase in the diameter of cavities decreased the stability of the upstream face dramatically for all examined locations in a horizontal direction; however, this effect was less on the downstream side. The results also showed that variations in the location of cavities in the horizontal direction have a greater effect on the stability than those in the vertical direction. The results revealed that increasing shear strength parameters of embankment does not reduce the influence of cavities on stability when those cavities are in critical locations.

Originality/value

A numerical model has been developed to simulate the effects of cavities on the stability of slopes in water-retaining structures/earth dams. The stability of earth dam slopes on upstream and downstream sides under rapid drawdown conditions considering various cavity effects, including their existence, diameter and location, were numerically analysed.
Three-stage quantitative approach of understanding household adaptation decisions in rural Cambodia
Authors: Jiao Xi , Zheng Yuan , Liu Zhen
Published: January 2020

Purpose

A better understanding of the processes that shape households’ adaptation decisions is essential for developing pertinent policies locally, thereby enabling better adaptation across scales and multiple stakeholders. This paper aims to examine the determinants of household decisions to adapt, it is also possible to target factors that facilitate or constrain adaptation. This helps to identify key components of current adaptive capacity, which leads to important insights into households’ competence to adapt in the future.

Design/methodology/approach

This paper takes a full-pledged approach examining factors and processes that shape households’ climate adaptation decision-making in rural Cambodia at three levels: adaptation status, adaptation intensity and choices of adaptation strategy. The three-stage analyses are materialized by applying the double hurdle model and multivariate probit model, which provides a potential way to systematically assess household adaptation decision-making in rural settings.

Findings

Results show a high level of involvement in adaptation among local households who are facing multiple stressors including climatic risks. The findings suggest that perceived climate change influence households’ decisions in both adaptation status and intensity. Access to financial credit, farmland size, water availability and physical asset holdings are identified as key factors promoting the adoption of more adaptation measures. To facilitate adaptation, collective effort and support at community level is important in providing knowledge based climate information dissemination and early warning systems. Public sector support and development aid programs should focus on positive triggers for targeted community and household adaptation.

Originality/value

The study, to the authors’ best knowledge, is one of the first studies to investigate the determinants of local adaptation decision-making systematically in Cambodia. It also provides a comprehensive approach to improve understanding of adaptation decision-making processes by exploring how various capital assets are associated with different stages of adaptation decisions. The findings contribute to policy implications enlightening adaptation planning at multi-scales with knowledge of key factors, which enhance local adaptive capacity to reduce climate change vulnerability.
Supervisor conflict management climate and emotion recognition skills
Authors: Way Kirsten A. , Jimmieson Nerina J. , Bordia Prashant
Published: January 2020

Purpose

Groups’ perceptions of their supervisors’ conflict management styles (CMSs) can have important implications for well-being. Rather than being examined in isolation, supervisor CMSs need to be considered in the context of supervisors’ emotional ability and the amount of conflict in workgroups. This paper aims to investigate the three-way interactions between group-level perceptions of supervisor CMSs (collaborating, yielding, forcing), supervisor emotion recognition skills and group relationship conflict in predicting collective employee burnout.

Design/methodology/approach

Group-level hierarchical multiple regressions were conducted with 972 teaching professionals nested in 109 groups.

Findings

The positive association between supervisor yielding climate and collective employee burnout was evident when supervisor emotion recognition was low but absent when supervisor emotion recognition was high. Groups with high supervisor forcing climate and high supervisor emotion recognition experienced lower group burnout, an effect evident at high but not low relationship conflict.

Practical implications

Supervisors have a critical – and challenging – role to play in managing conflict among group members. The detrimental effects of supervisor yielding and forcing climates on collective employee burnout are moderated by personal (supervisor emotion recognition) and situational (the level of relationship conflict) variables. These findings have practical implications for how supervisors could be trained to handle conflict.

Originality/value

This research challenges traditional notions that supervisor yielding and forcing CMSs are universally detrimental to well-being.
Status differences in interpersonal strain and job resources at work
Authors: Wallace Jean Elizabeth , Buchanan Tom
Published: January 2020

Purpose

This study aims to explore how status differences relate to strained working relationships with co-workers and clients. Two statuses, gender and occupation, are examined using data from veterinarians and animal health technologists (AHTs). Competing perspectives regarding exposure to stressful relationships and access and effectiveness of work-related resources are considered.

Design/methodology/approach

An explanatory sequential mixed-methods design is used that combines quantitative survey data with open-ended qualitative data. The survey data are used to examine how interpersonal strain and access to work-related resources vary by status. The qualitative data are used to illustrate how strain is experienced by these workers and aids in interpreting the quantitative findings.

Findings

Status is linked to interpersonal client strain and access to resources. Challenging work is widely available to all three groups, but is more beneficial in reducing higher status veterinarians’ client strain. Autonomy is a scarce resource for the lowest status group (female AHTs), yet appears effective in reducing co-worker strain for everyone. Unexpectedly, work overload and market concerns appear to aggravate work-related strain and greater numbers of the lowest status group exacerbates interpersonal tensions with clients.

Originality/value

This paper contributes by examining stressful interactions experienced by two occupations who work side-by-side in the same employment settings, but who vary significantly by gender representation and occupational status. The authors argue that in addition to gender and occupational status, the organizational health of employing clinics and the feminization of veterinary practice may offer insights into how status differences are related to interpersonal conflict experienced in these work places.