bluuebunny/crossref_metadata_2025 huggingface dataset:
An open state of a voltage-gated sodium channel involving a π-helix and conserved pore-facing Asparagine
Authors: Choudhury Koushik , Kasimova Marina A. , McComas Sarah , Howard Rebecca J , Delemotte Lucie
Published: July 2021

Voltage-gated sodium (Nav) channels play critical roles in propagating action potentials and otherwise manipulating ionic gradients in excitable cells. These channels open in response to membrane depolarization, selectively permeating sodium ions until rapidly inactivating. Structural characterization of the gating cycle in this channel family has proved challenging, particularly due to the transient nature of the open state. A structure from the bacterium Magnetococcus marinus Nav (NavMs) was initially proposed to be open, based on its pore diameter and voltage-sensor conformation. However, the functional annotation of this model, and the structural details of the open state, remain disputed. In this work, we used molecular modeling and simulations to test possible open-state models of NavMs. The full-length experimental structure, termed here the α-model, was consistently dehydrated at the activation gate, indicating an inability to conduct ions. Based on a spontaneous transition observed in extended simulations, and sequence/structure comparison to other Nav channels, we built an alternative π-model featuring a helix transition and the rotation of a conserved asparagine residue into the activation gate. Pore hydration, ion permeation and state-dependent drug binding in this model were consistent with an open functional state. This work thus offers both a functional annotation of the full-length NavMS structure, and a detailed model for a stable Nav open state, with potential conservation in diverse ion-channel families.
Retinal vibrations in bacteriorhodopsin are mechanically harmonic but electronically anharmonic: evidence from overtone and combination bands
Authors: Lorenz-Fonfria Victor A. , Yagi Kiyoshi , Ito Shota , Kandori Hideki
Published: July 2021

Vibrations of the chromophore in the membrane protein bacteriorhodopsin (BR), a protonated Schiff base retinal, have been studied for decades, both by resonance Raman and by infrared (IR) difference spectroscopy. In spite the light-induced IR difference spectrum between the K intermediate (13-cis retinal) and the initial BR state (all-trans retinal) being first published almost 40 years ago, we present here unreported bands in the 2500 to 1800 cm−1 region. We show that the bands between 2500 and 2300 cm−1 originate from overtone and combination transitions of retinal C-C stretches. We assigned some of the newly reported bands below 2300 cm−1 to the combination of retinal C-C stretches with methyl rocks and with hydrogen-out-of-plane vibrations. Remarkably, experimental C-C overtone bands appeared at roughly twice the wavenumber of their fundamentals, with anharmonic mechanical constants ≤ 3.5 cm−1, and in some cases of ∼1 cm−1. Comparison of combination and fundamental bands indicates that most of the mechanical coupling constants are also very small. Despite the mechanical quasi-harmonicity of the C-C stretches, the area of their overtone bands was only ∼50 to ∼100 times smaller than of their fundamental bands. We concluded that electronic anharmonicity, the second mechanism giving intensity to overtone bands, must be particularly high for the retinal C-C stretches. We corroborated the assignments of negative bands in the K-BR difference spectrum by ab initio anharmonic spectral calculations of all-trans retinal in BR, which also reproduced reasonably well the small experimental anharmonic and coupling mechanical constants. Yet, and in spite accounting for both mechanical and electronic anharmonicities, the intensity of overtone C-C transitions was underestimated by a factor of 4 to 20, indicating room for improvement in state-of-the-art anharmonic vibrational calculations.
Insights from spatial measures of intolerance to identify pathogenic variants in developmental and epileptic encephalopathies
Authors: Silk M , De Sá A , Olshansky M , Ascher D B
Published: July 2021

Developmental and epileptic encephalopathies (DEEs) are a group of epilepsies with early onset and severe symptoms that sometimes lead to death. While a number of genes have been successfully implicated, it remains challenging to identify causative mutations within these genes from the background variation present in all individuals due to disease heterogeneity. Our ability to detect likely pathogenic variants has continued to improve as in silico predictors of deleteriousness have advanced. We investigate their use in prioritising likely pathogenic variants in epileptic encephalopathy patient whole exome sequences and show that the inclusion of structure-based predictors of intolerance improve upon previous attempts to demonstrate enrichment within epilepsy genes.
Comparing cortex-wide gene expression patterns between species in a common reference frame
Authors: Englund Mackenzie , James Sebastian S. , Bottom Riley , Huffman Kelly J. , Wilson Stuart P. , Krubitzer Leah A.
Published: July 2021

Advances in sequencing techniques have made comparative studies of gene expression a current focus for understanding evolutionary and developmental processes. However, insights into the spatial expression of genes have been limited by a lack of robust methodology. We therefore developed a set of algorithms for quantifying and comparing tissue-wide spatial patterns of gene expression within and across species. Here we apply these algorithms to compare cortex-wide expression of Id2 and RZRβ mRNA in early postnatal mice and voles. We show that neocortical patterns of Id2 expression are moderately conserved between species, but that the degree of conservation varies by cortical layer and area. By comparison, patterns of RZRβ expression are highly conserved in somatosensory areas, and more variable between species in visual and auditory areas. We consider if these differences reflect independent evolution in the 35 million years since the last common ancestor.
Multi-tier mechanics control stromal adaptations in swelling lymph nodes
Authors: Assen Frank P. , Hons Miroslav , Hauschild Robert , Shamipour Shayan , Abe Jun , Kaufmann Walter A. , Costanzo Tommaso , Krens Gabriel , Brown Markus , Ludewig Burkhard , Hippenmeyer Simon , Stein Jens V. , Heisenberg Carl-Philipp , Hannezo Edouard , Luther Sanjiv A. , Sixt Michael
Published: July 2021

Lymph nodes (LNs) comprise two main structural elements: Fibroblastic reticular cells (FRCs) that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. While LNs are fairly stable in size during homeostatic conditions, immunological challenge causes more than 10-fold increase in size within only a few days. How a solid organ can accommodate such extreme volumetric changes is poorly understood. Here, we characterize the biomechanics of LN swelling on the cellular and organ scale. We identify lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing FRCs and their associated conduits to stretch. After an initial phase of relaxation, FRCs sense the resulting strain via cell matrix adhesions, which coordinates local growth and remodeling of the stromal network. While the expanded FRC network adopts its typical configuration, a massive fibrotic reaction of the organ capsule sets in and counters further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multi-tier fashion.
Machine Learning of Pseudomonas aeruginosa transcriptomes identifies independently modulated sets of genes associated with known transcriptional regulators
Authors: Rajput Akanksha , Tsunemoto Hannah , Sastry Anand V. , Szubin Richard , Rychel Kevin , Sugie Joseph , Pogliano Joe , Palsson Bernhard O.
Published: July 2021

The transcriptional regulatory network (TRN) of Pseudomonas aeruginosa plays a critical role in coordinating numerous cellular processes. We extracted and quality controlled all publicly available RNA-sequencing datasets for P. aeruginosa to find 281 high-quality transcriptomes. We produced 83 new RNAseq data sets under critical conditions to generate a comprehensive compendium of 364 transcriptomes. We used this compendium to reconstruct the TRN of P. aeruginosa using independent component analysis (ICA). We identified 104 independently modulated sets of genes (called iModulons), among which 81 (78%) reflect the effects of known transcriptional regulators. We show that iModulons: 1) play an important role in defining the genomic boundaries of biosynthetic gene clusters (BGCs); 2) show increased expression of the BGCs and associated secretion systems in conditions that emulate cystic fibrosis (CF); 3) show the presence of a novel BGC named RiPP (bacteriocin producer) which might have a role in worsening CF outcomes; 4) exhibit the interplay of amino acid metabolism regulation and central metabolism across carbon sources, and 5) clustered according to their activity changes to define iron and sulfur stimulons. Finally, we compare the iModulons of P. aeruginosa with those of E. coli to observe conserved regulons across two gram negative species. This comprehensive TRN framework covers almost every aspect of the transcriptional regulatory machinery in P. aeruginosa, and thus could prove foundational for future research of its physiological functions.
Exploratory extracellular vesicle-bound miRNA profiling to identify candidate biomarkers of chronic alcohol drinking in non-human primates
Authors: Lewis Sloan A. , Doratt Brianna , Sureshchandra Suhas , Pan Tianyu , Gonzalez Steven W. , Shen Weining , Grant Kathleen A. , Messaoudi Ilhem
Published: July 2021

Background

Long-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it is challenging to determine whether alcohol use should be considered a risk factor during diagnosis and treatment. We lack reliable biomarkers of alcohol use that could be used to determine drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNA (EV-miRNA) have been discovered to be consistent biomarkers of conditions including cancer and liver disease.

Methods

In this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 non-human primates after 12 months of voluntary ethanol drinking.

Results

We identified a list of up- and downregulated EV-miRNA candidate biomarkers of both heavy drinking as well as those positively correlated with ethanol dose. We further overexpressed these candidate miRNA in control primary peripheral immune cells to assess potential functional mechanisms of these EV-miRNA. We identified that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased inflammatory TNFα or IL-6 production in PBMC after stimulation.

Conclusion

This exploratory study identified several EV-miRNA that could serve as biomarkers of long-term alcohol drinking as well as provided a mechanism for alcohol-induced peripheral inflammation.
The swine spatiotemporal H3K27ac spectrum provides novel resources for exploring gene regulation related to complex traits and fundamental biological process
Authors: Zhu Yaling , Zhou Zhimin , Huang Tao , Zhang Zhen , Li Wanbo , Ling Ziqi , Jiang Tao , Yang Jiawen , Yang Siyu , Xiao Yanyuan , Charlier Carole , Georges Michel , Yang Bin , Huang Lusheng
Published: July 2021

The limited knowledge of genomic non-coding and regulatory regions has limited our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterize the spatiotemporal landscape of putative enhancers and promoters and their target genes by combining H3K27ac targeted ChIP-Seq and RNA-Seq in fetal (day 74-75 pc) and adult (day 132-150 pn) tissues (brain, liver, heart, muscle and small intestine) sampled from Asian aboriginal Bamaxiang and European highly selected Large White pigs of both sexes. We identify 101,290 H3K27ac peaks marking 18,521 promoters and 82,769 enhancers, including peaks that are active across all tissues and developmental stages could indicate safe harbors for exogenous gene insertion, and tissue and developmental-stage specific peaks that regulate genes pathways matching tissue and developmental stage specific physiological functions. We found H3K27ac and DNA methylation in the promoter region of the XIST gene may involve in X chromosome inactivation, and demonstrate utility of the present resource to reveal regulatory patterns of known causal genes and to prioritize candidate causal variants for complex traits in pigs. We have developed a web browser to improve the accessibility of the results (http://39.108.231.116/browser/?genome=susScr11).
Outcome-selective reinstatement is predominantly context-independent, and associated with c-Fos activation in the posterior dorsomedial striatum
Authors: Abiero Arvie R. , Ali Zaid , Vissel Bryce , Bradfield Laura A.
Published: July 2021

Research from human and animal studies has found that responding that has been successfully reduced following treatment can return upon exposure to certain contexts. An individual in recovery from alcohol use disorder, for example, might relapse to drinking upon visiting their favourite bar. However, most of these data have been derived from experiments involving a single (active) response, and the context-dependence of returned responding in situations involving choice between multiple actions and outcomes is less well-understood. We thus investigated how outcome-selective reinstatement – a procedure involving choice between multiple actions – was affected by altering the physical context in rats. In Experiment 1, rats were trained over 6 days to press a left lever for one food outcome (pellets or sucrose) and a right lever for the other outcome. Then, rats received an extinction session in either the same context (A) as lever press training, or in a different context (B). Rats were tested immediately (5 minutes) after extinction in Context A or B such that there were four groups in total: AAA, ABB, ABA, and AAB. Reinstatement testing consisted of one food outcome being delivered ‘freely’ (i.e. unearned by lever pressing and unsignalled by cues) to the food magazine every 4 minutes in the following order: Sucrose, Pellet, Pellet, Sucrose. Selective reinstatement was considered intact if pellet delivery increased pressing selectively on the pellet lever, and sucrose delivery selectively increased pressing on the sucrose lever. This result (Reinstated > Nonreinstated) was observed for rats in group AAA and ABB, but not rats in groups ABA and AAB. Experiment 2 was conducted identically, except that rats received two extinction sessions over two days and tested one day later. This time, all groups demonstrated intact outcome-selective reinstatement regardless of context. Analysis of c-Fos expression in several brain regions revealed that only c-Fos expression in the posterior dorsomedial striatum (pDMS) was related to intact reinstatement performance. Overall, these results suggest that outcome-selective reinstatement is predominantly context-independent, and that intact reinstatement is related to neuronal activity in the pDMS.

Highlights

Outcome-selective reinstatement is predominantly context-independent

Outcome-selective reinstatement is entirely context-independent after multiple extinction sessions

Outcome-selective reinstatement increases c-Fos expression in dorsomedial striatum

c-Fos expression in orbitofrontal cortex and dorsal hippocampus is unaffected by selective reinstatement.
Systems analysis of immune responses to attenuated P. falciparum malaria sporozoite vaccination reveals excessive inflammatory signatures correlating with impaired immunity
Authors: Du Ying , Hertoghs Nina , Duffy Fergal J. , Carnes Jason , McDermott Suzanne M. , Neal Maxwell L. , Schwedhelm Katharine V. , McElrath M. Juliana , De Rosa Stephen C. , Aitchison John D. , Stuart Kenneth D.
Published: July 2021

Immunization with radiation-attenuated sporozoites (RAS) can confer sterilizing protection against malaria, although the mechanisms behind this protection are incompletely understood. We performed a systems biology analysis of samples from the Immunization by Mosquito with Radiation Attenuated Sporozoites IMRAS) trial, which comprised P. falciparum RAS-immunized (PfRAS), malaria-naive participants whose protection from malaria infection was subsequently assessed by controlled human malaria infection (CHMI). Blood samples collected after initial PfRAS immunization were analyzed to compare immune responses between protected and non-protected volunteers leveraging integrative analysis of whole blood RNA-seq, high parameter flow cytometry, and single cell CITEseq of PBMCs. This analysis revealed differences in early innate immune responses indicating divergent paths associated with protection. In particular, elevated levels of inflammatory responses early after the initial immunization were detrimental for the development of protective adaptive immunity. Specifically, non-classical monocytes and early type I interferon responses induced within 1 day of PfRAS vaccination correlated with impaired immunity. Non-protected individuals also showed an increase in Th2 polarized T cell responses whereas we observed a trend towards increased Th1 and T-bet+ CD8 T cell responses in protected individuals. Temporal differences in genes associated with natural killer cells suggest an important role in immune regulation by these cells. These findings give insight into the immune responses that confer protection against malaria and may guide further malaria vaccine development.
Competitive advantage of oral streptococci for colonization of the middle ear mucosa
Authors: Jacob Kristin M. , Reguera Gemma
Published: July 2021

The intermittent aeration of the middle ear seeds its mucosa with saliva aerosols and selects for a distinct community of commensals adapted to the otic microenvironment. We gained insights into the selective forces that enrich for specific groups of oral migrants in the middle ear mucosa by investigating the phylogeny and physiology of 19 strains enriched (Streptococcus) or transiently present (Staphylococcus, Neisseria and actinobacterial Micrococcus and Corynebacterium) in otic secretions. Phylogenetic analyses of full length 16S rRNA sequences resolved close relationships between the streptococcal strains and oral commensals as well as between the transient migrants and known nasal and oral species. Physiological functions that facilitate mucosal colonization (swarming motility, surfactant production) and nutrition (mucin and protein degradation) were widespread in all the otic cultivars, as was the ability of most of the isolates to grow both aerobically and anaerobically. However, streptococci stood out for their enhanced biofilm-forming abilities under oxic and anoxic conditions and for their efficient fermentation of mucosal substrates into lactate, a key metabolic intermediate in the otic trophic webs. Additionally, the otic streptococci inhibited the growth of common otopathogens, an antagonistic interaction that could exclude competitors and protect the middle ear mucosa from infections by transient pathobionts. These adaptive traits allow streptococcal migrants to colonize the otic mucosa and grow microcolonies with syntrophic anaerobic partners, establishing trophic webs with other commensals similar to those formed by the oral ancestors in buccal biofilms.

Importance

The identification of a diverse microbiome in otic secretions from healthy young adults challenged the entrenched dogma of middle ear sterility and underscored previously unknown roles for oral commensals in the seeding of otic biofilms. By comparing the physiology of novel lineages of streptococci and transient (peri)oral species isolated from otic secretions, we identified adaptive behaviors that allow specific oral streptococcal species to successfully colonize the mucosa of the middle ear. We also describe antagonistic properties of the otic streptococci that help them outcompete transient nasal and oral migrants, including known otopathogens. This knowledge is important to predictively understand the functionality of the otic communities, their interactions with the host mucosa and the outcome of infections.
Construction of transcript regulation mechanism prediction models based on binding motif environment of transcription factor AoXlnR in Aspergillus oryzae
Authors: Oka Hiroya , Kojima Takaaki , Kato Ryuji , Ihara Kunio , Nakano Hideo
Published: July 2021

Recent study revealed that there are thousands of genes that remain unaffected by increased AoXlnR expression, despite the presence of one or more AoXlnR-binding motifs in their promoter region. Given this knowledge, we designed this study to construct several predictive models for determining whether a gene can exhibit a differential response to changes in AoXlnR expression. These models were constructed using 3D DNA shape information determined using the sequence around the AoXlnR binding motifs with classification as functional or nonfunctional. These models were created using a support vector machine followed by the evaluations designed to determine whether these DNA shape-based models can correctly classify functional motifs in terms of area under the receiver operating characteristic curve. The results showed that the differential expression levels of genes located downstream of the AoXlnR motif are closely related to specific DNA shape information around the binding motifs. Furthermore, we found that the parameters contributing to differential expressions differed depending on the number of motifs in the promoter region by comparing the prediction models using regions with only one binding DNA motif and those with multiple binding DNA motifs.

Author Summary

DNA-binding transcription factors (TFs) play a central role in transcriptional regulation mechanisms, mainly through their specific binding to target sites on the genome and regulation of the expression of downstream genes. Therefore, a comprehensive analysis of the function of these TFs will lead to the understanding of various biological mechanisms. However, the functions of TFs in vivo are diverse and complicated, and the identified binding sites on the genome are not necessarily involved in the regulation of downstream gene expression. In this study, we investigated whether DNA structural information around the binding site of transcription factors can be used to predict the involvement of the binding site in the regulation of the expression of genes located downstream of the binding site. Specifically, we calculated the structural parameters based on the DNA shape around the DNA binding motif located upstream of the gene whose expression is directly regulated by the transcription factor AoXlnR from Aspergillus oryzae, and showed that the presence or absence of expression regulation can be predicted from the sequence information with high accuracy by machine learning incorporating these parameters.
Spatial correlation of embedded nanowires probed by X-ray off-Bragg scattering of the host matrix
Authors: Tran Thomas , Weng Xiaorong , Hennes Marcel , Demaille Dominique , Coati Alessandro , Vlad Alina , Garreau Yves , Sauvage-Simkin Michèle , Sacchi Maurizio , Vidal Franck , Zheng Yunlin
Published: July 2021

It is shown that information on the spatial correlation of nano-objects embedded in a crystalline matrix can be retrieved by analysing the X-ray scattering around the Bragg reflections of the host matrix. Data are reported for vertically aligned Ni and CoNi alloy nanowires (NWs) in an SrTiO3 matrix. When the Bragg condition is fulfilled for the matrix and not for the NWs, the latter can be approximated by voids, and the scattering around the matrix reflections contains information on the self-correlation of the NWs (i.e. on their diameter d) and on the correlation between NWs (interdistance D). Nondestructive synchrotron X-ray diffraction data provide information on these values averaged over large areas, complementing local transmission electron microscopy observations. The measurements show that off-Bragg scattering around the matrix reflections can be exploited to study the spatial correlation and morphology of embedded nano-objects, independently of their crystallinity or strain or the presence of defects.
Growing a thriving international community for small-angle scattering through collaboration
Authors: Trewhella Jill
Published: July 2021

Small-angle scattering emerged as a tool for studying noncrystalline structures from early observations around 1930 that there was a relationship between the extent of the scattering and the size of the scattering object. André Guinier, a leading figure in the development of the field, noted in his summary findings from the first Conference on Small Angle Scattering in 1958 that the technique would be of value to study `submicroscopical inhomogeneities' and further provided a means of `observation [that had] in the past restricted the field of application of the X-ray method.' In 1965 the first of what became a highly successful series of Small-Angle Scattering (SAS) meetings held approximately every three years took place in Syracuse, NY, USA, and many of these ongoing meetings published their proceedings and highlights in the International Union of Crystallography (IUCr) Journal of Applied Crystallography. Since the early 2000s, the relationship between the international SAS community represented at the triennial SAS meetings and the IUCr has been strengthened and deepened through formal cooperation and collaboration in a number of mutually beneficial activities that have supported the growth and health of the field and the IUCr.
Thermodynamics of lattice vibrations in non-cubic crystals: the zinc structure revisited
Authors: Tomaschitz Roman
Published: July 2021

A phenomenological model of anisotropic lattice vibrations is proposed, using a temperature-dependent spectral cutoff and varying Debye temperatures for the vibrational normal components. The internal lattice energy, entropy and Debye–WallerBfactors of non-cubic elemental crystals are derived. The formalism developed is non-perturbative, based on temperature-dependent linear dispersion relations for the normal modes. The Debye temperatures of the vibrational normal components differ in anisotropic crystals; their temperature dependence and the varying spectral cutoff can be inferred from the experimental lattice heat capacity andBfactors by least-squares regression. The zero-point internal energy of the phonons is related to the low-temperature limits of the mean-squared vibrational amplitudes of the lattice measured by X-ray and γ-ray diffraction. A specific example is discussed, the thermodynamic variables of the hexagonal close-packed zinc structure, including the temperature evolution of theBfactors of zinc. In this case, the lattice vibrations are partitioned into axial and basal normal components, which admit largely differingBfactors and Debye temperatures. The second-orderBfactors defining the non-Gaussian contribution to the Debye–Waller damping factors of zinc are obtained as well. Anharmonicity of the oscillator potential and deviations from the uniform phonon frequency distribution of the Debye theory are modeled effectively by the temperature dependence of the spectral cutoff and Debye temperatures.
On Borromean links and related structures
Authors: O'Keeffe Michael , Treacy Michael M. J.
Published: July 2021

The creation of knotted, woven and linked molecular structures is an exciting and growing field in synthetic chemistry. Presented here is a description of an extended family of structures related to the classical `Borromean rings', in which no two rings are directly linked. These structures may serve as templates for the designed synthesis of Borromean polycatenanes. Links of n components in which no two are directly linked are termed `n-Borromean' [Liang & Mislow (1994). J. Math. Chem.
16, 27–35]. In the classic Borromean rings the components are three rings (closed loops). More generally, they may be a finite number of periodic objects such as graphs (nets), or sets of strings related by translations as in periodic chain mail. It has been shown [Chamberland & Herman (2015). Math. Intelligencer, 37, 20–25] that the linking patterns can be described by complete directed graphs (known as tournaments) and those up to 13 vertices that are vertex-transitive are enumerated. In turn, these lead to ring-transitive (isonemal) n-Borromean rings. Optimal piecewise-linear embeddings of such structures are given in their highest-symmetry point groups. In particular, isonemal embeddings with rotoinversion symmetry are described for three, five, six, seven, nine, ten, 11, 13 and 14 rings. Piecewise-linear embeddings are also given of isonemal 1- and 2-periodic polycatenanes (chains and chain mail) in their highest-symmetry setting. Also the linking of n-Borromean sets of interleaved honeycomb nets is described.
Piecewise-linear embeddings of knots and links with rotoinversion symmetry
Authors: O'Keeffe Michael , Treacy Michael M. J.
Published: July 2021

This article describes the simplest members of an infinite family of knots and links that have achiral piecewise-linear embeddings in which linear segments (sticks) meet at corners. The structures described are all corner- and stick-2-transitive – the smallest possible for achiral knots.
Structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states
Authors: Maciunas Lina J. , Porter Nadia , Lee Paula J. , Gupta Kushol , Loll Patrick J.
Published: July 2021

Vancomycin has historically been used as a last-resort treatment for serious bacterial infections. However, vancomycin resistance has become widespread in certain pathogens, presenting a serious threat to public health. Resistance to vancomycin is conferred by a suite of resistance genes, the expression of which is controlled by the VanR–VanS two-component system. VanR is the response regulator in this system; in the presence of vancomycin, VanR accepts a phosphoryl group from VanS, thereby activating VanR as a transcription factor and inducing expression of the resistance genes. This paper presents the X-ray crystal structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states at resolutions of 2.3 and 2.0 Å, respectively. Comparison of the two structures illustrates that phosphorylation of VanR is accompanied by a disorder-to-order transition of helix 4, which lies within the receiver domain of the protein. This transition generates an interface that promotes dimerization of the receiver domain; dimerization in solution was verified using analytical ultracentrifugation. The inactive conformation of the protein does not appear intrinsically unable to bind DNA; rather, it is proposed that in the activated form DNA binding is enhanced by an avidity effect contributed by the receiver-domain dimerization.
The β-link motif in protein architecture
Authors: Leader David P. , Milner-White E. James
Published: July 2021

The β-link is a composite protein motif consisting of a G1β β-bulge and a type II β-turn, and is generally found at the end of two adjacent strands of antiparallel β-sheet. The 1,2-positions of the β-bulge are also the 3,4-positions of the β-turn, with the result that the N-terminal portion of the polypeptide chain is orientated at right angles to the β-sheet. Here, it is reported that the β-link is frequently found in certain protein folds of the SCOPe structural classification at specific locations where it connects a β-sheet to another area of a protein. It is found at locations where it connects one β-sheet to another in the β-sandwich and related structures, and in small (four-, five- or six-stranded) β-barrels, where it connects two β-strands through the polypeptide chain that crosses an open end of the barrel. It is not found in larger (eight-stranded or more) β-barrels that are straightforward β-meanders. In some cases it initiates a connection between a single β-sheet and an α-helix. The β-link also provides a framework for catalysis in serine proteases, where the catalytic serine is part of a conserved β-link, and in cysteine proteases, including Mpro of human SARS-CoV-2, in which two residues of the active site are located in a conserved β-link.
Social capital and the shadow economy: a Bayesian analysis of the BRICS
Authors: Duong Tien Ha My , Nguyen Thi Anh Nhu , Nguyen Van Diep
Published: July 2021

Purpose

The paper aims to examine the impact of social capital on the size of the shadow economy in the BIRCS countries over the period 1995–2014.

Design/methodology/approach

The authors employ the Bayesian linear regression method to uncover the relationship between social capital and the shadow economy. The method applies a normal distribution for the prior probability distribution while the posterior distribution is determined using the Markov chain Monte Carlo technique.

Findings

The results indicate that the unemployment rate and tax burden positively affect the size of the shadow economy. By contrast, corruption control and trade openness are negatively associated with the development of this informal sector. Moreover, the paper's primary finding is that social capital represented by social trust and tax morale can hinder the size of the shadow economy.

Research limitations/implications

This study is limited to the case of the BRICS countries for the period 1995–2014. The determinants of the shadow economy in different groups of countries can be heterogeneous. Moreover, social capital is a multidimensional concept that may consist of various components. This difficulty of measuring the social capital calls for further research on the relationship between other dimensions of social capital and the shadow economy.

Originality/value

Many studies investigate the effect of economic factors on the size of the shadow economy. This paper applies a new approach to discover the issue. Notably, the authors use the Bayesian linear regression method to analyze the relationship between social capital and the shadow economy in the BRICS countries.
Identifying tourist profiles to reduce overtourism: the case of a cultural destination
Authors: Martínez Suárez Rocío , Castañeda García José Alberto , Rodríguez Molina Miguel Ángel
Published: July 2021

Purpose

Knowing the behavior of tourists visiting cultural destinations enables better management of tourist flows, a better understanding of areas with greater tourist density and an opportunity to decongest popular neighborhoods. The purpose of this study is to segment tourists according to their spatio-temporal behavior and identify the primary variables that characterize the resulting segments, which will help urban destinations prevent problems arising from the saturation of tourists in certain areas.

Design/methodology/approach

To do this, this paper analyzes the behavior of tourists visiting the southeastern Spanish city of Granada, one of the most highly visited cultural tourism destinations. The data analysis used the methodology of sequence alignment which is used to identify segments as a function of their contained elements and the order in which these appear.

Findings

The results demonstrate the existence of three segments with different behavioral patterns: the “explorer tourists” segment, the “non-traditional cultural tourists” segments and the “typical cultural tourists” segment. These segments show differences in the concentration of their visits. This study discovered that the segments that visit a greater number of destination areas are those with less cultural orientation, higher travel budgets and younger and more frequent visitors.

Originality/value

In the segmentation not only keep in mind the visited areas, but the order in which they were visited as well. In addition, one should consider the time that each tourist remains in each relevant zone of the destination, given that the visiting time is an important variable to assess the congestion of an area.
Digital civic learning in schools: Youth perspectives and experiences
Authors: DiGiacomo Daniela K.
Published: July 2021

Purpose

While living in the information age is not new, the continued spread of dis/mis/information in tandem with rising partisanship has made clear the educational need for robust and critical information and media literacy education (Bulger and Davison, 2018; Garcia et al., 2021; Reich, 2018; Wineburg and McGrew, 2016). Given that most young people (and adults) today get their information and news about the world through online sources, including social media (Pew Research Center, 2018; Garcia et al., 2021), it is imperative for the health of the American democracy that students’ school-based civic learning opportunities include digital civic learning, too. This paper aims to offer a study into one such schooling landscape in a large and diverse public school district in the USA.

Design/methodology/approach

A mixed-method approach – including an online survey and face-to-face group interviews – was used to understand the opportunity landscape more broadly and glean insight into the texture and nuance of youth perspectives and experiences on digital civic learning.

Findings

Analysis of data reveals a dearth of consistent and routine opportunities for digital civic learning within the Rio Public School District context.

Originality/value

Empirical research that examines and makes visible students’ lived experiences and perspectives with digital civic information is essential if as educators and researchers, the authors are to successfully design for more and better of these experiences.
Dexterity analysis and intelligent trajectory planning of redundant dual arms for an upper body humanoid robot
Authors: Sulaiman Shifa , Sudheer A.P.
Published: July 2021

Purpose

Most of the redundant dual-arm robots are singular free, dexterous and collision free compared to other robotic arms. This paper aims to analyse the workspace of redundant arms to study the manipulability. Furthermore, multi-layer perceptron (MLP) algorithm is used to determine the various joint parameters of both the upper body redundant arms. Trajectory planning of robotic arms is carried out with the help of inverse solutions obtained from the MLP algorithm.

Design/methodology/approach

In this paper, the kinematic equations are derived from screw theory approach and inverse kinematic solutions are determined using MLP algorithm. Levenberg–Marquardt (LM) and Bayesian regulation (BR) techniques are used as the backpropagation algorithms. The results from two backpropagation techniques are compared for determining the prediction accuracy. The inverse solutions obtained from the MLP algorithm are then used to optimize the cubic spline trajectories planned for avoiding collision between arms with the help of convex optimization technique. The dexterity of the redundant arms is analysed with the help of Cartesian workspace of arms.

Findings

Dexterity of redundant arms is analysed by studying the voids and singular spaces present inside the workspace of arms. MLP algorithms determine unique solutions with less computational effort using BR backpropagation. The inverse solutions obtained from MLP algorithm effectively optimize the cubic spline trajectory for the redundant dual arms using convex optimization technique.

Originality/value

Most of the MLP algorithms used for determining the inverse solutions are used with LM backpropagation technique. In this paper, BR technique is used as the backpropagation technique. BR technique converges fast with less computational time than LM method. The inverse solutions of arm joints for traversing optimized cubic spline trajectory using convex optimization technique are computed from the MLP algorithm.
The congruence of mental models in entrepreneurial teams – implications for performance and satisfaction in teams operating in an emerging economy
Authors: Ziemiański Paweł , Stankiewicz Katarzyna , Tomczak Michał T. , Krawczyk-Bryłka Beata
Published: July 2021

Purpose

The paper aims to explore the relationship between the congruence of mental models held by the members of entrepreneurial teams operating in an emerging economy (Poland) and entrepreneurial outcomes (performance and satisfaction).

Design/methodology/approach

The data obtained from 18 nascent and 20 established entrepreneurial teams was analysed to answer hypotheses. The research was quantitative and was conducted using an online questionnaire. Data was collected from each of the teams at two stages. Members of entrepreneurial teams were surveyed independently, which allowed measuring the congruence of their mental models pertaining to running a venture.

Findings

Findings reveal that team members’ mental model congruence is significantly related to financial performance and members’ satisfaction in the case of established entrepreneurial teams. However, in the case of nascent teams, there is no relationship between analysed variables.

Practical implications

Implications for theory and practice are offered with a special emphasis on entrepreneurship education. The concept of team mental model congruence is proposed to be included in training of nascent entrepreneurial teams, experienced companies and students.

Originality/value

The concept of team mental models investigated by the authors has been underexplored in entrepreneurship research. Results indicate that at least in some entrepreneurial teams, team mental models’ congruence is related to obtained outcomes. The paper proposes that principles of effectuation and causation can serve as the lens through which the mental model pertaining to running a venture can be analysed. It allows expanding studies on the congruence of team mental models in entrepreneurial teams beyond the strategic consensus.
The Covid-19 impact on financial crime and regulatory compliance in Malaysia
Authors: Jamil Ainul Huda , Mohd Sanusi Zuraidah , Yaacob Najihah Marha , Mat Isa Yusarina , Tarjo Tarjo
Published: July 2021

Purpose

The purpose of this paper is to provide a conceptual discussion and analysis of the Covid-19 impact on financial crime and regulatory compliance. The analysis is conducted to make a comparison of the financial crime and regulatory compliance patterns before and after the Covid-19 pandemic occurred.

Design/methodology/approach

This paper contextualises the impact of Covid-19 on financial crime and regulatory compliance. Moreover, this paper explores different ways of conceptualising the Covid-19 impacts in terms of financial crimes and regulatory compliance patterns based on the surveys by PricewaterhouseCoopers and Deloitte.

Findings

The Covid-19 pandemic has brought both challenges and opportunities to financial crime and regulatory compliance. In the aspects of financial crime patterns, this study found a reduction in physical crime whilst on the other hand increment in cybercrime. Nevertheless, this study discovered regulatory compliance not at a satisfactory stage even before the Covid-19 pandemic, let alone during the pandemic.

Practical implications

This study implies that the financial institutions must work together to combat the risks of financial crimes, not only amongst the institutions but also with the regulators. Digitalisation and robust risk management need to be improved at a massive level to beat the criminals’ high fintech skills and systems. The initiatives of fund packages from the governments to assist the companies especially the small firms need to be fully used by the companies to improve regulatory compliance.

Originality/value

Whilst some studies discussed the impact of Covid-19 on the economy, there are still scarce resources on the comparative analysis on the financial crime and regulatory compliance, not to mention the before and after effect of the Covid-19 pandemic. This is the first paper to integrate the issues surrounding the Covid-19 impact, financial crimes and regulatory compliance in Malaysia.
Preliminary insights on green criminology in Malaysia
Authors: Bilu Redvin , Darus Faizah , Yusoff Haslinda , Mohamed Intan Salwani
Published: July 2021

Purpose

The purpose of this paper is to examine the extent of environmental offences committed in Malaysia charged under the Environmental Quality Act 1974 (EQA1974).

Design/methodology/approach

This study used secondary data of the environmental court cases report by the Department of Environment (DOE) Malaysia from 2008 until 2016 to examine the nature of environmental offences based on the Treadmill of Production (ToP) approach.

Findings

In comparison with the GDP growth (Department of Statistic Malaysia, 2016), the findings support ToP argument that as far as the treadmill accelerates, the more would be the environmental crime committed. However, all offences charged were weighted more on the ecological additions rather than ecological withdrawn. The trend analysis showed a decreasing trend for all types of offences committed, reflecting that Malaysia's regulatory authorities are committed to fighting against environmental crime perpetrators. Therefore, all parties must be made to internalise the values of conducting business sustainably.

Originality/value

This paper is the first that examines the environmental offences committed in Malaysia using the ToP approach to analyse the nature of the crime committed in Malaysia associated with the growing literature of Green Criminology.
Corruption and international development: a review of project management challenges
Authors: Harnois Yanik , Gagnon Stéphane
Published: July 2021

Purpose

The outcomes and quality of international development projects (IDPs) remain highly controversial, especially with perception of corruption by various stakeholders. This study aims to integrate findings from both social and administrative sciences to focus attention on the governance challenges involved in both business and public administration of such projects. It also asks to what extent Project Management (PM) methods can effectively be harmonized with broader anti-corruption initiative in both donor and receiving countries.

Design/methodology/approach

Taking a transdisciplinary viewpoint, this study proposes a review and synthesis of the literature on the theoretical, methodological, and epistemological issues in researching corruption as a construct in PM as applied to IDPs.

Findings

Some experts recognize the inefficacy of applying classical PM tools and processes. By contrasting the literature, this study concludes that an alternative approach to overcome the taboos and prejudice in studying corruption is to ask a different research question. As opposed to studying “who and why” about corruption occurrences (ex-post), given the challenge of unveiling its practices and motivations, PM researchers can to ask instead “where and how” it occurs and help understand methods to mitigate its effects on projects (ex-ante).

Originality/value

A research agenda is proposed for the several disciplines and fields concerned with solving this phenomenon. To guide PM research on development projects, focusing on the “where and how” of corruption requires addressing how actors build their knowledge management capabilities and address the social and cultural challenges inherent to IDPs.