bluuebunny/crossref_metadata_2025 huggingface dataset:
A synthetic ancestral Kinesin-13 depolymerises microtubules faster than any natural depolymerising kinesin
Authors: Belsham Hannah R. , Alghamdi Hanan M. , Dave Nikita , Rathbone Alexandra J. , Wickstead Bill , Friel Claire T.
Published: April 2022

The activity of a kinesin is largely determined by the ~350 residue motor domain and this region alone is sufficient to classify a kinesin as a member of a particular family. The Kinesin-13 family are a group of microtubule depolymerising kinesins and are vital regulators of microtubule length. Members of this family are critical to spindle assembly and chromosome segregation in both mitotic and meiotic cell division and play crucial roles in cilium length control and neuronal development. To better understand the evolution of microtubule depolymerisation activity in the Kinesin-13 family, we created a synthetic ancestral Kinesin-13 motor domain. This phylogenetically-inferred ancestral motor domain is the sequence predicted to have existed in the common ancestor of the Kinesin-13 family. Here we show that the ancestral Kinesin-13 motor depolymerises stabilised microtubules faster than any previously tested depolymerase. This potent activity is more than an order of magnitude faster than the most highly studied Kinesin-13, MCAK and allows the ancestral Kinesin-13 to depolymerise doubly-stabilised microtubules that are unaffected by MCAK. These data suggest that the ancestor of the Kinesin-13 family was a ‘super depolymeriser’ and that members of the Kinesin-13 family have evolved away from this extreme depolymerising activity to provide more controlled microtubule depolymerisation activity in extant cells.
Coarsening dynamics can explain meiotic crossover patterning in both the presence and absence of the synaptonemal complex
Authors: Fozard John A , Morgan Chris , Howard Martin
Published: April 2022

The shuffling of genetic material facilitated by meiotic crossovers is a critical driver of genetic variation. Therefore, the number and positions of crossover events must be carefully controlled. InArabidopsis, an obligate crossover and repression of nearby crossovers on each chromosome pair are abolished in mutants that lack the synaptonemal complex (SC), a conserved protein scaffold. We use mathematical modelling and quantitative super-resolution microscopy to explore and mechanistically explain meiotic crossover pattering inArabidopsislines with full, incomplete or abolished synapsis. Forzyp1mutants, which lack an SC, we develop a coarsening model in which crossover precursors globally compete for a limited pool of the pro-crossover factor HEI10, with dynamic HEI10 exchange mediated through the nucleoplasm. We demonstrate that this model is capable of quantitatively reproducing and predictingzyp1experimental crossover patterning and HEI10 foci intensity data. Additionally, we find that a model combining both SC- and nucleoplasm-mediated coarsening can explain crossover patterning in wild-typeArabidopsisand inpch2mutants, which display partial synapsis. Together, our results reveal that regulation of crossover patterning in wild-typeArabidopsisand SC defective mutants likely act through the same underlying coarsening mechanism, differing only in the spatial compartments through which the pro-crossover factor diffuses.
A diet-independent zebrafish model for NAFLD recapitulates patient lipid profiles and offers a system for small molecule screening
Authors: Singh Manoj K , Yadav Rohit , Bhaskar Akash Kumar , Sengupta Shantanu , Sachidanandan Chetana
Published: April 2022

Non-alcoholic Fatty Liver Disease (NAFLD) or pathological hepatic lipid overload, is considered to affect obese individuals. However, NAFLD in lean individuals is prevalent, especially in South Asian population. The pathophysiology of lean NAFLD is not well understood and most animal models of NAFLD use the high-fat diet paradigm. To bridge this gap, we have developed a diet-independent model of NAFLD in zebrafish. We have previously showed that chronic systemic inflammation causes metabolic changes in the liver leading to hepatic fat accumulation in an IL6 overexpressing (IL6-OE) zebrafish model. In the present study, we compared the hepatic lipid composition of adult IL6-OE zebrafish to the controls and found an accumulation of saturated triacylglycerols and a reduction in the unsaturated triacylglycerol species reminiscent of NAFLD patients. Zebrafish is an ideal system for chemical genetic screens. We tested whether the hepatic lipid accumulation in the IL6-OE is responsive to chemical treatment. We found that PPAR-gamma agonist Rosiglitazone, known to reduce lipid overload in the high fat diet models of NAFLD, could ameliorate the fatty liver phenotype of the IL6-OE fish. Rosiglitazone treatment reduced the accumulation of saturated lipids and showed a concomitant increase in unsaturated TAG species in our inflammation-induced NAFLD model. Our observations suggest that the IL6-OE model can be effective for small molecule screening to identify compounds that can reverse hepatic lipid accumulation, especially relevant to lean NAFLD.
INRI-seq enables global cell-free analysis of translation initiation and off-target effects of antisense inhibitors
Authors: Hör Jens , Jung Jakob , Đurica-Mitić Svetlana , Barquist Lars , Vogel Jörg
Published: April 2022

Ribosome profiling (Ribo-seq) is a powerful method for the transcriptome-wide assessment of protein synthesis rates and the study of translational control mechanisms. Yet, Ribo-seq also has limitations. These include difficulties with detection of low abundance transcripts and analysis of translation-modulating molecules such as antibiotics, which are often toxic or challenging to deliver into living cells. Here, we have developedin vitroRibo-seq (INRI-seq), a cell-free method to analyze the translational landscape of a fully customizable synthetic transcriptome. UsingEscherichia colias an example, we show how INRI-seq can be used to analyze the translation initiation sites of a transcriptome of interest. We also study the global impact of direct translation inhibition by antisense peptide nucleic acid (PNA) to analyze PNA off-target effects. Overall, INRI-seq presents a scalable, sensitive method to study translation initiation in a transcriptome-wide manner without the potentially confounding effects of extracting ribosomes from living cells.
Separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis
Authors: Wang Lei , Kruse Thomas , López-Méndez Blanca , Zhang Yuqing , Song Chunlin , Zhu Lei , Li Bing , Fang Jing , Lu Zhimin , Nilsson Jakob , Zhang Gang
Published: April 2022

The Bub1 and BubR1 kinetochore proteins support proper chromosome segregation and mitotic checkpoint activity. Bub1 and BubR1 are paralogues with Bub1 being a kinase while BubR1 localizes the PP2A-B56 protein phosphatase to kinetochores in humans. Whether this separation of kinase and phosphatase activity is important is unclear as some organisms integrate both activities into one Bub protein. Here we engineer human Bub1 and BubR1 proteins integrating kinase and phosphatase activities into one protein and show that these do not support normal mitotic progression. A Bub1-PP2A-B56 complex can supports chromosome alignment but results in impairment of the checkpoint due to dephosphorylation of the Mad1 binding site in Bub1. Furthermore, a chimeric BubR1 protein containing the Bub1 kinase domain induces delocalized H2ApT120 phosphorylation resulting in reduction of centromeric hSgo2 and chromosome segregation errors. Collectively, these results argue that the separation of kinase and phosphatase activities within the Bub complex is required for balancing its functions in the checkpoint and chromosome alignment.
Autophagy Increases Occludin Levels to Enhance Intestinal Paracellular Tight Junction Barrier
Authors: Saha Kushal , Ganapathy Ashwinkumar Subramenium , Wang Alexandria , Morris Nathan Michael , Suchanec Eric , Yochum Gregory , Koltun Walter , Ding Wei , Nighot Meghali , Ma Thomas , Nighot Prashant
Published: April 2022

Background and Aim

Functional loss of paracellular tight junction (TJ) barrier of the gut epithelium and mutations in autophagy genes are factors potentiating inflammatory bowel disease (IBD). Previously we showed the role of autophagy in enhancing the TJ barrier via claudin-2 degradation, however, its role in the regulation of the barrier-forming protein occludin remains unknown. Here, we investigate the role of autophagy in the regulation of occludin and its role in inflammation-mediated TJ barrier loss.

Methods

Pharmacological and genetic tools were used to study the effect of autophagy on occludin levels and localization, and the role of the MAPK pathway.

Results

Autophagy induction using pharmacological activators and nutrient starvation increased total occludin levels in different epithelial cells. Starvation enriched membrane occludin levels and reduced paracellular inulin flux in Caco-2 cells. Starvation-induced TJ barrier enhancement was contingent on the presence of occludin as OCLN-/- nullified its TJ barrier enhancing effect. Autophagy inhibited the constitutive degradation of occludin and protected against inflammation-induced TJ barrier loss. Starvation-induced TJ barrier enhancement was prevented by inhibition of autophagy. Autophagy enhanced the phosphorylation of ERK-1/2. Inhibition of these kinases in Caco-2 cells and human intestinal mucosa inhibited the protective effects of autophagy. In-vivo, autophagy induction by rapamycin increased occludin levels in mouse intestines and protected against LPS and TNF-α-induced TJ barrier loss. Additionally, acute Atg7 knockout in adult mice decreased intestinal occludin levels, increasing baseline colonic TJ-permeability and exacerbating the effect of DSS-induced colitis.

Conclusion

Our data suggest a novel role of autophagy in promoting the intestinal TJ barrier by increasing occludin levels in an ERK1/2 MAPK-dependent mechanism.

Graphical abstract
Condensation of LINE-1 is required for retrotransposition
Authors: Sil Srinjoy , Boeke Jef D , Holt Liam J
Published: April 2022

LINE-1 (L1) is the only autonomously active retrotransposon in the human genome, and accounts for 17% of the human genome. The L1 mRNA encodes two proteins, ORF1p and ORF2p. ORF1p is a homotrimeric RNA-binding protein that plays a critical role in assembling functional L1 ribonucleoprotein (RNP) complexes. Here we show that condensation of ORF1p is required for L1 retrotransposition. Using a combination of biochemical reconstitution and live-cell imaging, we demonstrate that RNA binding, electrostatic interactions, and trimer conformational dynamics together tune the properties of ORF1p assemblies to allow for efficient L1 condensate formation in cells. Furthermore, we directly relate the dynamics of ORF1p assembly to the ability to complete the entire retrotransposon life-cycle. Mutations that prevented ORF1 condensation led to loss of retrotransposition activity, while orthogonal restoration of coiled-coil conformational flexibility rescued both condensation and retrotransposition. Based on these observations, we propose that ORF1p oligomerization on L1 RNA drives the formation of a dynamic L1 condensate that is essential for retrotransposition.
Using soybean historical field trial data to study genotype by environment variation and identify mega-environments with the integration of genetic and non-genetic factors
Authors: Krause Matheus D , Dias Kaio O G , Singh Asheesh K , Beavis William D
Published: April 2022

1

Soybean (Glycine max(L.) Merr.) provides plant-based protein for global food production and is extensively bred to create cultivars with greater productivity in distinct environments. Plant breeders evaluate new soybean genotypes using multi-environment trials (MET). The application of MET assumes that trial locations provide representative environmental conditions that cultivars are likely to encounter when grown by farmers. In addition, MET are important to depict the patterns of genotype by environment interactions (GEI). To evaluate GEI for soybean seed yield and identify mega-environments (ME), a retrospective analysis of 39,006 data points from experimental soybean genotypes evaluated in preliminary and uniform field trials conducted by public plant breeders from 1989-2019 was considered. ME were identified from phenotypic information from the annual trials, geographic, soil, and meteorological records at the trial locations. Results indicate that yield variation was mostly explained by location and location by year interactions. The static portion of the GEI represented 26.30% of the total yield variance. Estimates of variance components derived from linear mixed models demonstrated that the phenotypic variation due to genotype by location interaction effects was greater than genotype by year interaction effects. A trend analysis indicated a two-fold increase in the genotypic variance between 1989-1995 and 1996-2019. Furthermore, the heterogeneous estimates of genotypic, genotype by location, genotype by year, and genotype by location by year variances, were encapsulated by distinct probability distributions. The observed target population of environments can be divided into at least two and at most three ME, thereby suggesting improvements in the response to selection can be achieved when selecting directly for clustered (i.e., regions, ME) versus selecting across regions. Clusters obtained using phenotypic data, latitude, and soil variables plus elevation, were the most effective. In addition, we published the R package SoyURT which contains the data sets used in this work.

2

Highlights

Mega-environments can be identified with phenotypic, geographic, and meteorological data.

Reliable estimates of variances can be obtained with proper analyses of historical data.

Genotype by location was more important than genotype by year variation for seed yield.

The trend in genotype by environment variances was captured in probability distributions.
Highly Parallelized, Multicolor Optogenetic Recordings of Cellular Activity for Therapeutic Discovery Applications in Ion Channels and Disease-associated Excitable Cells
Authors: Borja Gabriel B , Zhang Hongkang , Harwood Benjamin N , Jacques Jane , Grooms Jennifer , Chantre Romina , Zhang Dawei , Barnett Adam , Werley Christopher A , Lu Yang , Nagle Steven , McManus Owen B , Dempsey Graham T
Published: April 2022

Optogenetic assays provide a flexible, scalable and information rich approach to probe compound effects for ion channel drug targets in both heterologous expression systems and associated disease relevant cell types. Despite the potential utility and growing adoption of optogenetics, there remains a critical need for compatible platform technologies with the speed, sensitivity, and throughput to enable their application to broader drug screening applications. To address this challenge, we developed the Swarm™, a custom designed optical instrument for highly parallelized, multicolor measurements in excitable cells, simultaneously recording changes in voltage and calcium activities at high temporal resolution under optical stimulation. The compact design featuring high power LEDs, large numerical aperture optics, and fast photodiode detection enables all-optical individual well readout of 24-wells simultaneously from multi-well plates while maintaining sufficient temporal resolution to probe millisecond response dynamics. The Swarm delivers variable intensity blue-light optogenetic stimulation to enable membrane depolarization and red or lime-light excitation to enable fluorescence detection of the resulting changes in membrane potential or calcium levels, respectively. The Swarm can screen ~10,000 wells / day in 384-well format, probing complex pharmacological interactions via a wide array of stimulation protocols. To evaluate the Swarm screening system, we optimized a series of heterologous optogenetic spiking HEK293 cell assays for several voltage-gated sodium channel subtypes including Nav1.2, Nav1.5, and Nav1.7. The Swarm was able to record pseudo-action potentials stably across all 24 objectives and provided pharmacological characterization of diverse sodium channel blockers. We performed a Nav1.7 screen of 200,000 small molecules in a 384-well plate format with all 560 plates reaching a Z’≥0.5. As a demonstration of the versatility of the Swarm, we also developed an assay measuring cardiac action potential and calcium waveform properties simultaneously under paced conditions using human induced pluripotent stem (iPS) cell-derived cardiomyocytes as an additional counter screen for cardiac toxicity. In summary, the Swarm is a novel high-throughput all-optical system capable of collecting information-dense data from optogenetic assays in both heterologous and iPS cell-derived models, which can be leveraged to drive diverse therapeutic discovery programs for nervous system disorders and other disease areas involving excitable cells.
Olfactory receptor neurons generate multiple response motifs, increasing coding space dimensionality
Authors: Kim Brian , Haney Seth , Millan Ana P. , Joshi Shruti , Aldworth Zane , Rulkov Nikolai , Kim Alexander T. , Bazhenov Maxim , Stopfer Mark
Published: April 2022

Odorants binding to olfactory receptor neurons (ORNs) trigger bursts of action potentials, providing the brain with its only experience of the olfactory environment. Our recordings made in vivo from locust ORNs showed odor-elicited firing patterns comprise four distinct response motifs, each defined by a reliable temporal profile. Different odorants could elicit different response motifs from a given ORN, a property we term motif switching. Further, each motif undergoes its own form of sensory adaptation when activated by repeated plume-like odor pulses. A computational model constrained by our recordings revealed that organizing responses into multiple motifs provides substantial benefits for classifying odors and processing complex odor plumes: each motif contributes uniquely to encode the plume’s composition and structure. Multiple motifs and motif switching further improve odor classification by expanding coding dimensionality. Our model demonstrated these response features could provide benefits for olfactory navigation, including determining the distance to an odor source.
DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness
Authors: Carrier Arnaud , Desjobert Cécile , Ponger Loïc , Lamant Laurence , Bustos Matias , Torres-Ferreira Jorge , Henrique Rui , Jeronimo Carmen , Lanfrancone Luisa , Delmas Audrey , Favre Gilles , Daunay Antoine , Busato Florence , Hoon Dave S.B. , Tost Jörg , Etievant Chantal , Riond Joëlle , Arimondo Paola B.
Published: April 2022

Aberrant DNA methylation is a well-known feature of tumours and has been associated with metastatic melanoma. However, since melanoma cells are highly heterogeneous, it has been challenging to use affected genes to predict tumour aggressiveness, metastatic evolution, and patients’ outcomes. We hypothesized that common aggressive hypermethylation signatures should emerge early in tumorigenesis and should be shared in aggressive cells, independent of the physiological context under which this trait arises.

We compared paired melanoma cell lines with the following properties:(i)each pair comprises one aggressive counterpart and its parental cell line, and(ii)the aggressive cell lines were each obtained from different host and their environment (human, rat, and mouse), though starting from the same parent cell line. Next, we developed a multi-step genomic pipeline that combines the DNA methylome profile with a chromosome cluster-oriented analysis.

A total of 229 differentially hypermethylated genes were commonly found in the aggressive cell lines. Genome localization analysis revealed hypermethylation peaks and clusters, identifying eight hypermethylated gene promoters for validation in tissues from melanoma patients.

Five CpG identified in primary melanoma tissues were transformed into a DNA methylation score that can predict survival (Log-rank test,p=0.0008). This strategy is potentially universally applicable to other diseases involving DNA methylation alterations.
Phylotranscriptomics Reveals the Reticulate Evolutionary History of a Widespread Diatom Species Complex
Authors: Çiftçi Ozan , Alverson Andrew J. , van Bodegom Peter , Roberts Wade R. , Mertens Adrienne , Van de Vijver Bart , Trobajo Rosa , Mann David G. , Pirovano Walter , van Eijk Iris , Gravendeel Barbara
Published: April 2022

In contrast to surveys based on a few genes that often provide limited taxonomic resolution, transcriptomes provide a wealth of genomic loci that can resolve relationships among taxonomically challenging lineages. Diatoms are a diverse group of aquatic microalgae that includes important bioindicator species and many such lineages. One example is Nitzschia palea, a widespread species complex with several morphologically based taxonomic varieties, some of which are critical pollution indicators. Morphological differences among the varieties are subtle and phylogenetic studies on a few genes fail to resolve their evolutionary relationships. We conducted morphometric and transcriptome analyses of 10 Nitzschia palea strains to resolve the relationships among strains and taxonomic varieties. Nitzschia palea was resolved into three clades, one of which corresponds to a group of strains with narrow linear-lanceolate valves. The other morphological group recovered in the shape outline analysis was not monophyletic and consisted of two clades. Subsequent gene-tree concordance analyses and phylogenetic network estimations revealed patterns of incomplete lineage sorting and gene flow between intraspecific lineages. We detected reticulated evolutionary patterns among lineages with different morphologies and a resulting putative recent hybrid. Our study shows that phylogenomic analyses of many unlinked nuclear loci, complemented with morphometrics, can resolve complex evolutionary histories of recently diverged species complexes.
Hierarchical Computational Modeling and Dynamic Network Analysis of Allosteric Regulation in the SARS-CoV-2 Spike Omicron Trimer Structures: Omicron Mutations Cooperate to Allosterically Control Balance of Protein Stability and Conformational Adaptability
Authors: Verkhivker Gennady M. , Agajanian Steve , Kassab Ryan , Krishnan Keerthi
Published: April 2022

Structural and computational studies of the Omicron spike protein in various functional states and complexes provided important insights into molecular mechanisms underlying binding, high transmissibility, and escaping immune defense. However, the regulatory roles and functional coordination of the Omicron mutations are poorly understood and often ignored in the proposed mechanisms. In this work, we explored the hypothesis that the SARS-CoV-2 spike protein can function as a robust allosterically regulated machinery in which Omicron mutational sites are dynamically coupled and form a central engine of the allosteric network that regulates the balance between conformational plasticity, protein stability, and functional adaptability. In this study, we employed coarse-grained dynamics simulations of multiple full-length SARS-CoV-2 spike Omicron trimers structures in the closed and open states with the local energetic frustration analysis and collective dynamics mapping to understand the determinants and key hotspots driving the balance of protein stability and conformational adaptability. We have found that the Omicron mutational sites at the inter-protomer regions form regulatory clusters that control functional transitions between the closed and open states. Through perturbation-based modeling of allosteric interaction networks and diffusion analysis of communications in the closed and open spike states, we quantify the allosterically regulated activation mechanism and uncover specific regulatory roles of the Omicron mutations. The network modeling demonstrated that Omicron mutations form the inter-protomer electrostatic bridges that connect local stable communities and function as allosteric switches of signal transmission. The results of this study are consistent with the experiments, revealing distinct and yet complementary role of the Omicron mutational sites as a network of hotspots that enable allosteric modulation of structural stability and conformational changes which are central for spike activation and virus transmissibility.
Bayesian Parameter Estimation for Dynamical Models in Systems Biology
Authors: Linden Nathaniel J. , Kramer Boris , Rangamani Padmini
Published: April 2022

Dynamical systems modeling, particularly via systems of ordinary differential equations, has been used to effectively capture the temporal behavior of different biochemical components in signal transduction networks. Despite the recent advances in experimental measurements, including sensor development and ‘-omics’ studies that have helped populate protein-protein interaction networks in great detail, systems biology modeling lacks systematic methods to estimate kinetic parameters and quantify associated uncertainties. This is because of multiple reasons, including sparse and noisy experimental measurements, lack of detailed molecular mechanisms underlying the reactions, and missing biochemical interactions. Additionally, the inherent nonlinearities with respect to the states and parameters associated with the system of differential equations further compound the challenges of parameter estimation. In this study, we propose a comprehensive framework for Bayesian parameter estimation and complete quantification of the effects of uncertainties in the data and models. We apply these methods to a series of signaling models of increasing mathematical complexity. Systematic analysis of these dynamical systems showed that parameter estimation depends on data sparsity, noise level, and model structure, including the existence of multiple steady states. These results highlight how focused uncertainty quantification can enrich systems biology modeling and enable additional quantitative analyses for parameter estimation.
Sensory conflict disrupts circadian rhythms in the sea anemone Nematostella vectensis
Authors: Berger Cory A. , Tarrant Ann M.
Published: April 2022

Circadian clocks infer time of day by integrating information from cyclic environmental factors called zeitgebers, including light and temperature. Single zeitgebers entrain circadian rhythms, but few studies have addressed how multiple, simultaneous zeitgeber cycles interact to affect clock behavior. Misalignment between zeitgebers (“sensory conflict”) can disrupt circadian rhythms, or alternatively clocks may privilege information from one zeitgeber over another. Existing studies are limited in the range of tested zeitgeber relationships, and also in their taxonomic breadth, which is restricted to insects and vertebrates among animals. Here, we show that temperature cycles entrain circadian locomotor rhythms in Nematostella vectensis, a model system for cnidarian circadian biology. We then conduct behavioral experiments across a comprehensive range of light and temperature cycles. Nematostella’s circadian behavior is disrupted by chronic sensory conflict, including disruption of the endogenous clock itself rather than a simple masking effect. Sensory conflict also disrupts the rhythmic transcriptome, with numerous genes losing rhythmic expression. However, many metabolic genes remained rhythmic and in-phase with temperature, and other genes even gained rhythmicity, implying that some rhythmic metabolic processes persist even when behavior is disrupted. Our results show that a cnidarian clock relies on information from light and temperature, rather than prioritizing one zeitgeber over the other. Although we identify limits to the clock’s ability to integrate conflicting sensory information, there is also a surprising robustness of behavioral and transcriptional rhythmicity.
A molecular substitutional disorder case study suitable for instruction: L
2CrII(THF)/L
2[(trimethylsilyl)methyl]CrIII (L is 2,5-bis{[(2,6-diisopropylphenyl)imino]methyl}pyrrol-1-ide)
Authors: Salisbury Brian A. , Young John F. , Theopold Klaus H. , Yap Glenn P. A.
Published: April 2022

A solution of CrII and CrIII complexes, bis(2,5-bis{[(2,6-diisopropylphenyl)imino]methyl}pyrrol-1-ido)(tetrahydrofuran)chromium(II)–bis(2,5-bis{[(2,6-diisopropylphenyl)imino]methyl}pyrrol-1-ido)[(trimethylsilyl)methyl]chromium(III) (0.88/0.12), [Cr(C30H38N3)2(C4H8O)]0.88[Cr(C30H38N3)2(C4H11Si)]0.12 or L
2CrII(THF)/L
2[(trimethylsilyl)methyl]CrIII (L = 2,5-bis{[(2,6-diisopropylphenyl)imino]methyl}pyrrol-1-ide and THF is tetrahydrofuran), in pentane crystallizes in the monoclinic space group P21/c. The structure obtained shows most of the atoms coincident but with THF disordered with the (trimethylsilyl)methyl ligand. Structures with this disorder, involving more than two or three atoms, seem to appear rarely in the literature; however, in this case, the data set is ideal for the crystallographic instruction of molecular substitution disorder.
Remarkable lives: Khia Stacey in conversation with Robert Hurst
Authors: Stacey Khia , Hurst Robert
Published: April 2022

Purpose

The purpose of this paper is to share Khia Stacey’s story.

Design/methodology/approach

Khia Stacey wrote a short piece detailing her journey, and she was then interviewed by Robert Hurst.

Findings

Khia Stacey spoke about experiencing trauma, facing difficulties within child and adolescent mental health services and how she chose to fight on.

Research limitations/implications

Recovery narratives such as the current one give the readers an overview of only a single person’s experiences. However, they allow the person with lived experience to explore their story in depth.

Practical implications

Khia Stacey stresses the importance of listening to service users and gives advice on how mental health professionals can better support those in services.

Social implications

There is so much to learn from a story such as Khia’s – for those who have had similar experiences and for those who work in mental health services.

Originality/value

This is the first time that Khia has chosen to share her unique story. Its value is apparent immediately upon reading it.
Bridging the marketing-finance divide: use of customer voice in managerial decision-making
Authors: Saxena Deepak , Brady Mairead , Lamest Markus , Fellenz Martin
Published: April 2022

Purpose

This study aims to provide more insight into how customer voice is captured and used in managerial decision-making at the marketing-finance interface. This study’s focus is on understanding how the customer voice, often communicated through online and social media platforms, is used in high-performing hotels.

Design/methodology/approach

This research is based on a case study of four high-performing Irish hotels. For each case, multiple informants, including marketing managers, general managers and finance managers, were interviewed and shadowed. Twenty seven decisions across the four cases were analysed to assess the use of customer voice in managerial decision-making.

Findings

Social media provides a stage that has empowered the customer voice because of the public nature of the interaction and the network effect. Customer voice is incorporated in managerial decision-making in three distinct ways – symbolically as part of an early warning system, for action-oriented operational decisions and to some extent in the knowledge-enhancing role for tactical decisions. While there is a greater appreciation among senior managers and the finance and accounting managers of the importance of customer voice, this study finds clear limits in its utilisation and more reliance on traditional finance and accounting data, especially in strategic decision-making.

Research limitations/implications

The cases belong to a highly visible open environment of hotels in an industry where customer voice has immediate and strong effects. The findings may not directly apply to industries characterised by a relatively more closed context such as banking or insurance. Moreover, the findings reflect the practices of high-performing hotels and do not necessarily capture the practices used in less successfully operating hotels.

Practical implications

While marketers need to enhance their ability to create a narrative that links the customer voice to revenue generation, finance managers also need to develop a skillset and adopt a mindset that appropriately reflects the influential role for customer voice in managerial decision-making.

Originality/value

Despite the linkage of marketing performance to business performance, there is limited research on the impact of customer information on managerial decision-making. This research provides insight into how customer voice is considered at the critical marketing-finance interface.
Diversity and ecology of Radiolaria in modern oceans
Authors: Biard Tristan
Published: April 2022

Among the many inhabitants of planktonic communities, several lineages have biomineralized intricate skeletons. These have existed for millions of years and include the Radiolaria, a group of marine protists, many of which bear delicate mineral skeletons of different natures. Radiolaria are well known for their paleontological signatures, but little is known about the ecology of modern assemblages. They are found from polar to tropical regions, in the sunlit layers of the ocean down to the deep and cold bathypelagic. They are closely involved in the biogeochemical cycles of silica, carbon and strontium sulfate, carrying important amounts of such elements to the deep ocean. However, relatively little is known on the actual extent of genetic diversity or biogeographic patterns. The rapid emergence and acceptance of molecular approaches have nevertheless led to major advances in our understanding of diversity within and evolutionary relationships between major radiolarian groups. Here, we review the state of knowledge relating to the classification, diversity and ecology of extant radiolarian orders, highlighting the substantial gaps in our understanding of the extent of their contribution to marine biodiversity and their role in marine food webs.
The impact and policy relevance of street lighting for crime prevention: A systematic review based on a half‐century of evaluation research
Authors: Welsh Brandon C. , Farrington David P. , Douglas Stephen
Published: April 2022

Research Summary

This article reports on an updated systematic review and meta‐analysis of the effects of street lighting interventions on crime in public places. Following Campbell Collaboration guidelines, it uses robust criteria for inclusion of studies, comprehensive search strategies to identify eligible studies, a detailed protocol for coding key study characteristics, and rigorous methods for analyzing studies. A total of 21 studies met the inclusion criteria, originating in four countries (United States, United Kingdom, Brazil, and South Korea) and covering almost 50 years (1974–2021). The review finds that street lighting interventions are associated with a significant desirable effect on total crime (14% reduction in treatment areas compared with comparable control areas); desirable effects are greater in studies that measured both night and day crimes than in studies that only measured night crimes; and street lighting is followed by a significant reduction in property crimes, but not in violent crimes.

Policy Implications

Compared to past years, it would seem that an even stronger case can be made today for street lighting interventions to be part of crime‐prevention policy. A larger body of high‐quality evaluation research, implemented in a range of high‐crime public places, some evidence of value for money, and a continued desirable impact on crime, especially property crime, all point to the policy relevance of street lighting interventions.
Rheological and tribological nature of flaxseed gum influenced by concentration and temperature and its application as a coating agent for potato chips
Authors: Safdar Bushra , Pang Zhihua , Liu Xinqi , Jatoi Mushtaque Ahmad , Rashid Muhammad Tayyab
Published: April 2022

Influence of different concentrations (0.5, 1.0, 2.0, and 3.0% w/v) and temperatures (4, 25, 50, and 75°C) on particle size distribution (PSD) and rheological and tribological characteristics of flaxseed gum (FSG) solutions was investigated. Besides, FSG dispersions (0.5, 1.0, and 2.0% w/v) were used as edible coating and their influence on the quality parameters (oil uptake, moisture loss, texture, and sensory properties) of fried potato chips was studied. All FSG dispersions revealed shear‐thinning nature and viscous properties (as G″ > G′) that were more dominant at higher concentrations and lower temperatures. The power–law model presented a good fit in demonstrating the flow behavior of FSG dispersions. Concentration was the variable that affected the tribology of FSG dispersions, while temperature had little effect on the tribology. Particle size distribution was increased with the increasing concentration of FSG. FSG dispersions as an edible coating effectively reduced the moisture loss, oil uptake, and hardness properties of potato chips.

Practical Application

Profiling the influence of concentration and temperature on the rheology and tribology of flaxseed gum is particularly valuable during food processing. The results predict the physical properties of coated potato chips that can support the potential application of flaxseed gum as a coating agent. Today's consumers prefer healthier food products with low caloric, higher fiber content, functional properties, and sensory qualities. Food industries can use FSG as a low‐cost natural coating material in terms of economic benefits, consumer acceptance, and providing an inordinate potential both for its protective effect and carrying functional compounds such as antioxidants in their coating matrix.
Prognostic value of preoperative plasma fibrinogen levels in resected stage I non‐small cell lung cancer
Authors: Mitsui Suguru , Tanaka Yugo , Doi Takefumi , Hokka Daisuke , Maniwa Yoshimasa
Published: April 2022

Background

The number of surgical procedures has increased among patients with early‐stage lung cancer. If the poor prognostic factors for stage I non‐small cell lung cancer (NSCLC) can be simply validated preoperatively, appropriate treatment will be provided. The current study aimed to evaluate the prognostic value of preoperative plasma fibrinogen levels in patients with resected stage I NSCLC.

Methods

We retrospectively analyzed the clinicopathological information of patients (n = 149) who underwent lobectomy for stage I NSCLC between May 2014 and July 2016. Data about peripheral blood analysis, histopathological finding, and follow‐up assessment results were collected from the databases. Patients were divided into the low and high fibrinogen groups. Univariate and multivariate analyses were performed to evaluate the predictors of recurrence and survival.

Results

Compared with the low fibrinogen group (<377 mg/dl), the high fibrinogen group (≥377 mg/dl) had a significantly greater number of male participants (p = 0.04), smokers (p < 0.001), and those with elevated cytokeratin antigen levels (p = 0.04), lymphatic invasion (p = 0.007), and squamous cell carcinoma (p < 0.001). Plasma fibrinogen level was considered a significant independent factor for recurrence and overall survival on both the univariate and multivariate analyses (p < 0.001 and p = 0.010) and the multivariate analysis alone (p = 0.020 and p < 0.012).

Conclusion

Preoperative plasma fibrinogen level might be a useful predictor of recurrence and survival in patients with stage I NSCLC. The treatment strategy for patients with high fibrinogen levels could be cautiously considered preoperatively.
Audit Risk Evaluation Using Data Envelopment Analysis with Ordinal Data
Authors: Amin Gholam R. , El‐Temtamy Osama , Garas Samy
Published: April 2022

This study examines the data envelopment analysis (DEA) model for audit risk evaluation which was initially developed by Bradbury and Rouse (2002) and reinterpreted by Davutyan and Kavut (2005). Bradbury and Rouse (2002) apply the standard DEA model for audit risk factors, including judgemental (ordinal) measures. In the presence of ordinal data, efficiency analysis in DEA requires appropriate models to be applied instead of the standard DEA model. Accordingly, audit risk evaluation based on the standard DEA model is not assessed appropriately because the risk factors are qualitative and ordinal measures. Hence, we employ an appropriate DEA model to accurately evaluate audit risk in the presence of ordinal data. In light of the prior two studies, our results demonstrate the appropriateness of the ordinal DEA model.
The use of digital footprints in the US mortgage market
Authors: Jayasuriya D Dulani , Ayaz Mohamed , Williams Michael
Published: April 2022

We study the rise of digital footprint (DF) users in the U.S. residential mortgage market. The proportion of lenders that use a borrower's DF has witnessed remarkable growth from 6% in 2013 to 34% in 2018 in a short span – according to our analysis. We show that the use of DFs can significantly reduce a lender's overall risk and that the use of DFs can result in considerable societal benefits, by reducing the overall discriminatory forces. In sum, we provide evidence that the informational advantage associated with using a borrower's DF far outweighs that of existing traditional lending methods.
Can B cell‐deficient patients rely on COVID‐19 vaccine‐induced T‐cell immunity?
Authors: Shree Tanaya
Published: April 2022

Anti‐CD20 antibody treatments prevent humoral responses to vaccines against severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccines, but the nature of T‐cell responses in this setting is less well understood. Riise et al. assess vaccine‐induced epitope‐specific CD8 T cell responses in patients with lymphoma recently treated with rituximab and find a wide range of responses, with the most recently treated patients frequently failing to respond, while others exhibit responses stronger than healthy controls. They suggest these epitopes among others could be used in a T cell‐targeted vaccine, and such strategies are indeed in clinical trials now.

Commentary on: Riise J, et al. Rituximab‐treated patients with lymphoma develop strong CD8 T‐cell responses following COVID‐19 vaccination. Br J Haematol. 2022;197:697‐708
Extralysosomal cathepsin B in central nervous system: Mechanisms and therapeutic implications
Authors: Ni Junjun , Lan Fei , Xu Yan , Nakanishi Hiroshi , Li Xue
Published: April 2022

Cathepsin B (CatB) is a typical cysteine lysosomal protease involved in a variety of physiologic and pathological processes. It is expressed in most cell types and is primarily localized within subcellular endosomal and lysosomal compartments. Emerging scientific evidence indicates that lysosomal leaked CatB is involved in mitochondrial stress, inflammasome activation, and nuclear senescence, but without the acidic environment. CatB is also secreted as a myokine, which is involved in muscle‐brain cross talk and neuronal dendritic remodeling. Lysosomal‐leaked and cellular‐secreted CatB functions are dependent on its enzymatic activity at a neutral pH. In the present review, we summarize the available experimental evidence that mechanistically links extralysosomal CatB to physiological and pathological functions in central nervous system, and their potential for use in therapeutic approaches.
The role of non‐discrimination in a world of discriminatory preferential trade agreements
Authors: Saggi Kamal , Wong Woan Foong , Yildiz Halis Murat
Published: April 2022

In a three‐country model of endogenous trade agreements, we study the implications of the most‐favoured‐nation (MFN) clause when countries are free to form discriminatory preferential trade agreements (PTAs). Under current rules of the World Trade Organization (WTO), although non‐member countries face discrimination at the hands of PTA members, they themselves are obligated to abide by MFN and treat PTA members in a non‐discriminatory fashion. The non‐discrimination constraint of MFN reduces the potency of a country's optimal tariffs and therefore its incentive for unilaterally opting out of trade liberalization. Thus, MFN can act as a catalyst for trade liberalization. However, when PTAs take the form of customs unions, the efficiency case for MFN as well as its pro‐liberalization effect is weaker because one country finds itself deliberately excluded by the other two as opposed to staying out voluntarily.
The Effect of Social Presence on Mentalizing Behavior
Authors: Morgan Emma J. , Carroll Daniel J. , Chow Constance K. C. , Freeth Megan
Published: April 2022

Our behavior is frequently influenced by those around us. However, the majority of social cognition research is conducted using socially isolated paradigms, without the presence of real people (i.e., without a “social presence”). The current study aimed to test the influence of social presence upon a measure of mentalizing behavior in adults. Study 1 used a first‐order theory of mind task; and study 2 used a second‐order theory of mind task. Both studies included two conditions: live, where the task protagonists were physically present acting out the task, or recorded, where the same task protagonists demonstrated the task in a video recording. In both experiments, participants were affected by the social presence and demonstrated significantly different patterns of behavior in response to the presence of real people. This study, therefore, highlights the critical importance of understanding the effect of a social presence in mentalizing research, and suggests that the inclusion of a social presence needs to be given strong consideration across social cognition paradigms.
A Computational Model of Context‐Dependent Encodings During Category Learning
Authors: Carvalho Paulo F. , Goldstone Robert L.
Published: April 2022

Although current exemplar models of category learning are flexible and can capture how different features are emphasized for different categories, they still lack the flexibility to adapt to local changes in category learning, such as the effect of different sequences of study. In this paper, we introduce a new model of category learning, the Sequential Attention Theory Model (SAT‐M), in which the encoding of each presented item is influenced not only by its category assignment (global context) as in other exemplar models, but also by how its properties relate to the properties of temporally neighboring items (local context). By fitting SAT‐M to data from experiments comparing category learning with different sequences of trials (interleaved vs. blocked), we demonstrate that SAT‐M captures the effect of local context and predicts when interleaved or blocked training will result in better testing performance across three different studies. Comparatively, ALCOVE, SUSTAIN, and a version of SAT‐M without locally adaptive encoding provided poor fits to the results. Moreover, we evaluated the direct prediction of the model that different sequences of training change what learners encode and determined that the best‐fit encoding parameter values match learners’ looking times during training.