bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Perfusion Assessment by Indocyanine Green Fluorescence Imaging for Minimally Invasive Rectal Cancer Surgery (EssentiAL trial)
Authors: Watanabe Jun , Takemasa Ichiro , Kotake Masanori , Noura Shingo , Kimura Kei , Suwa Hirokazu , Tei Mitsuyoshi , Takano Yoshinao , Munakata Koji , Matoba Shuichiro , Yamagishi Sigeru , Yasui Masayoshi , Kato Takeshi , Ishibe Atsushi , Shiozawa Manabu , Ishii Yoshiyuki , Yabuno Taichi , Nitta Toshikatsu , Saito Shuji , Saigusa Yusuke , Watanabe Masahiko ,   for the EssentiAL Trial Group
Published: May 2023

Objective:

The aim of the present randomized controlled trial was to evaluate the superiority of indocyanine green fluorescence imaging (ICG-FI) in reducing the rate of anastomotic leakage in minimally invasive rectal cancer surgery.

Background:

The role of ICG-FI in anastomotic leakage in minimally invasive rectal cancer surgery is controversial according to the published literature.

Methods:

This randomized, open-label, phase 3, trial was performed at 41 hospitals in Japan. Patients with clinically stage 0–III rectal carcinoma less than 12 cm from the anal verge, scheduled for minimally invasive sphincter-preserving surgery were preoperatively randomly assigned to receive a blood flow evaluation by ICG-FI (ICG+ group) or no blood flow evaluation by ICG-FI (ICG− group). The primary endpoint was the anastomotic leakage rate (grade A+B+C, expected reduction rate of 6%) analyzed in the modified intention-to-treat population.

Results:

Between December 2018 and February 2021, a total of 850 patients were enrolled and randomized. After the exclusion of 11 patients, 839 were subject to the modified intention-to-treat population (422 in the ICG+ group and 417 in the ICG− group). The rate of anastomotic leakage (grade A+B+C) was significantly lower in the ICG+ group (7.6%) than in the ICG− group (11.8%) (relative risk, 0.645; 95% confidence interval 0.422–0.987; P=0.041). The rate of anastomotic leakage (grade B+C) was 4.7% in the ICG+ group and 8.2% in the ICG− group (P=0.044), and the respective reoperation rates were 0.5% and 2.4% (P=0.021).

Conclusions:

Although the actual reduction rate of anastomotic leakage in the ICG+ group was lower than the expected reduction rate and ICG-FI was not superior to white light, ICG-FI significantly reduced the anastomotic leakage rate by 4.2%.
Comprehensive Cost Implications of Commercially Available Noninvasive Colorectal Cancer Screening Modalities
Authors: Allen Casey J , Bloom Nathan , Rothka Michael , Rao Pavan , Wagner Patrick L , Bartlett David L , Farah Katie , Chalikonda Sricharan
Published: May 2023

BACKGROUND:

There is an increasing usage of noninvasive screening modalities for colorectal cancer (CRC), primarily the fecal immunochemical test (FIT) and multi-target stool DNA test (Cologuard [CG]). The aim of this study was to determine the comprehensive, long-term cost implications of these noninvasive screening modalities.

STUDY DESIGN:

Using a national insurer-based administrative dataset, patients screened for CRC from January 1, 2019 to December 31, 2019 were analyzed. A hierarchical logic system was used to determine the primary screening modality for each patient. The total annual costs in US dollars ($) were extrapolated using number of patients screened, costs per test, screening intervals, and costs incurred from false results. Patients within our tumor registry diagnosed with CRC were matched to their claims data, and cancer stage distribution was compared.

RESULTS:

Of 119,334 members who underwent noninvasive screening, 38.1% underwent screening with FIT and 40.0% with CG. The combined annual cost for these 2 screening modalities was $13.7 million. By transitioning to FIT alone for all noninvasive screening, the total annual cost would decrease to $7.9 million, resulting in a savings of approximately $5.8 million per year. Additionally, by combining data from the network cancer registry and insurer-based claims dataset, we were able to match 533 individuals who underwent screening and were later diagnosed with CRC. The rate of early-stage (stage 0 to II) disease was found to be similar between those screened with FIT and CG (59.5% FIT vs 63.2% CG; p = 0.77).

CONCLUSIONS:

The adoption of FIT as the primary noninvasive CRC screening method has the potential to generate significant cost savings, and therefore, carries significant value implications for a large population health system.
An Atlas of Adaptive Evolution in Endemic Human Viruses
Authors: Kistler Kathryn E. , Bedford Trevor
Published: May 2023

Through antigenic evolution, viruses like seasonal influenza evade recognition by neutralizing antibodies elicited by previous infection or vaccination. This means that a person with antibodies well-tuned to an initial infection will not be protected against the same virus years later and that vaccine-mediated protection will decay. It is not fully understood which of the many endemic human viruses evolve in this fashion. To expand that knowledge, we assess adaptive evolution across the viral genome in 28 endemic viruses, spanning a wide range of viral families and transmission modes. We find that surface proteins consistently show the highest rates of adaptation, and estimate that ten viruses in this panel undergo antigenic evolution to selectively fix mutations that enable the virus to escape recognition by prior immunity. We compare overall rates of amino acid substitution between these antigenically-evolving viruses and SARS-CoV-2, showing that SARS-CoV-2 viruses are accumulating protein-coding changes at substantially faster rates than these endemic viruses.
The COVID-19 mRNA vaccine Comirnaty induces anaphylactic shock in an anti-PEG hyperimmune large animal model: Role of complement activation in cardiovascular, hematological and inflammatory mediator changes
Authors: Barta Bálint András , Radovits Tamás , Dobos Attila Balázs , Kozma Gergely Tibor , Mészáros Tamás , Berényi Petra , Facskó Réka , Fülöp Tamas Gyula , Merkely Béla , Szebeni János
Published: May 2023

Background

Comirnaty, Pfizer-BioNTech’s polyethylene-glycol (PEG)-containing Covid-19 vaccine, can cause hypersensitivity reactions (HSRs) in a small fraction of immunized people which can, very rarely, culminate in life-threatening anaphylaxis. A role of anti-PEG antibodies (Abs) has been proposed, but causality has not yet been proven in an animal model. This study aimed to provide such evidence using anti-PEG hyperimmune pigs (i.e., pigs displaying very high levels of anti-PEG Abs). We also sought to find evidence for the role of complement (C) activation and thromboxane A2 (TXA2) release in blood as contributing effects to anaphylaxis.

Methods

Pigs (n=6) were immunized with 0.1 mg/kg PEGylated liposome (Doxebo) i.v. the rise of anti-PEG IgG and IgM was measured in serial blood samples with ELISA. After 2-3 weeks, during the height of seroconversion, the animals were injected i.v. with 1/3 human vaccine dose (HVD) of Comirnaty, and the hemodynamic (PAP, SAP), cardiopulmonary (HR, EtCO2,), hematological parameters (WBC, granulocyte, lymphocyte, and platelet counts) and blood immune mediators (anti-PEG IgM and IgG Abs, C3a and TXA2) were measured as endpoints of HSRs.

Results

A week after immunization of 6 pigs with Doxebo, the level of anti-PEG IgM and IgG rose 5-10-thousands-fold in all animals, and they all developed anaphylactic shock to i.v. injection of 1/3 HVD of Comirnaty. The reaction, starting within 1 min, led to the abrupt decline of SAP along with maximal pulmonary hypertension, decreased pulse pressure amplitude, tachycardia, granulo- and thrombocytopenia, and paralleling rises of plasma C3a and TXB2 levels. These vaccine effects were not observed in non-immunized pigs.

Conclusions

Consistent with previous studies with PEGylated nano-liposomes, these data show a causal role of anti-PEG Abs in the anaphylaxis to Comirnaty. The reaction involves C activation, and, hence, it represents C activation-related pseudo-allergy (CARPA). The setup provides the first large-animal model for mRNA-vaccine-induced anaphylaxis in humans.
The interplay between neoantigens and immune cells in sarcomas treated with checkpoint inhibition
Authors: Anzar Irantzu , Malone Brandon , Samarakoon Pubudu , Vardaxis Ioannis , Simovski Boris , Fontenelle Hugues , Meza-Zepeda Leonardo A , Stratford Richard , Keung Emily Z , Burgess Melissa , Tawbi Hussein A. , Myklebost Ola , Clancy Trevor
Published: May 2023

Sarcomas are comprised of diverse bone and connective tissue tumors with few effective therapeutic options for locally advanced unresectable and/or metastatic disease. Recent advances in immunotherapy, in particular immune checkpoint inhibition (ICI), have shown promising outcomes in several cancer indications. Unfortunately, ICI therapy has provided only modest clinical responses and seems moderately effective in a subset of the diverse subtypes. To explore the immune parameters governing ICI therapy resistance or immune escape, we performed whole exome sequencing (WES) on tumors and their matched normal blood, in addition to RNA-seq from tumors of 31 sarcoma patients treated with pembrolizumab. We used advanced computational methods to investigate key immune properties, such as neoantigens and immune cell composition in the tumor microenvironment (TME). A multifactorial analysis suggested that expression of high quality neoantigens in the context of specific immune cells in the TME are key prognostic markers of progression-free survival (PFS). The presence of several types of immune cells, including T cells, B cells and macrophages, in the TME were associated with improved PFS. Importantly, we also found the presence of both CD8+ T cells and neoantigens together was associated with improved survival compared to the presence of CD8+ T cells or neoantigens alone. Interestingly, this trend was not identified with the combined presence of CD8+ T cells and TMB; suggesting that a combined CD8+ T cell and neoantigen effect on PFS was important. The outcome of this study may inform future trials that may lead to improved outcomes for sarcoma patients treated with ICI.
Endodermal BRD4 mediates epithelial-mesenchymal crosstalk during lung development
Authors: Liberti Derek C. , Wen Hongbo , Quansah Kwaku K. , Chandrasekaran Prashant , Pankin Josh , Michki Nigel S. , Jin Annabelle , Lu MinQi , Nieuwburgh Maureen Peers De , Young Lisa R. , Jain Rajan , Frank David B.
Published: May 2023

Lung morphogenesis relies on diverse cell intrinsic and extrinsic mechanisms to ensure proper cellular differentiation and compartmentalization. Using genetic mouse models, tissue explants, and transcriptomic analysis, we demonstrate that the epigenetic reader Bromodomain Containing Protein 4 (BRD4) is required for lung morphogenesis and perinatal survival. Endodermal BRD4 deletion impairs epithelial-mesenchymal crosstalk, leading to disrupted proximal-distal patterning and branching morphogenesis. These early defects result in dilated airways and the formation of cystic distal airway structures, containing both airway and alveolar features. Moreover, BRD4 deficient lungs exhibit abnormal airway and alveolar epithelial cell lineage allocation and differentiation. Restoration of SHH signaling partially rescues defects due to loss of BRD4, suggesting a role for BRD4 in regulating the SHH-FGF signaling axis. Together, these data identify the essential role of Brd4 in lung development to ensure proper intercellular crosstalk to enable proper lineage specification, identity, and maturation.
Dependent variable selection in phylogenetic generalized least squares regression analysis under Pagel’s lambda model
Authors: Chen Zheng-Lin , Guo Hong-Ji , Niu Deng-Ke
Published: May 2023

Phylogenetic generalized least squares (PGLS) regression is widely used to analyze evolutionary relationships between two traits. In contrast to the equal treatment of analyzed traits in conventional correlation methods such as Pearson and Spearman’s rank tests, we must designate one trait as the independent variable and the other as the dependent variable.

We retrieved an empirical dataset containing the optimal growth temperature, minimal doubling time, CRISPR-Cas, and prophage contents of 262 bacteria from a recent publication and conducted 16000 simulations of the evolution of two traits along a binary tree with 100 terminal nodes, using different models and variances. Correlations in these two datasets were examined by PGLS regression using Pagel’sλmodel.

By examining correlations in the empirical dataset, we found that switching independent and dependent variables resulted in conflicting results in 26.3% of cases. PGLS regression analysis of the 16000 simulated data showed that the frequency of conflicting outcomes from switching dependent and independent variables depends on the strength of the relationship between the two analyzed traits. Switching dependent and independent variables would strongly affect the parameter estimation of the PGLS regressions if the two variables differ significantly in their phylogenetic signals. To assess correlations in each simulation, we established a gold standard by analyzing changes in traits along phylogenetic branches. Next, we tested seven potential criteria for dependent variable selection: log-likelihood, Akaike information criterion,R2,p-value, Pagel’sλ, Blomberg et al.’sK, and the estimatedλin Pagel’sλmodel. We determined that the last three criteria performed equally well in selecting the dependent variable and were superior to the other four.

Since Pagel’sλand Blomberg et al.’sKvalues are indicators of phylogenetic signals, which are commonly calculated at the beginning of phylogenetic comparative studies, we suggest using the trait with a higherλorKvalue as the dependent variable for practicality in future PGLS regressions. In analyzing the evolutionary relationship between two traits, we should designate the trait with a stronger phylogenetic signal as the dependent variable even if it could logically assume the cause in the relationship.
Bearskin2 mediates the coordinated secretion of xylogalacturonan and root cap polygalacturonase in Arabidopsis border-like cells
Authors: Liu Zhongyuan , Wang Pengfei , Goh Tatsuaki , Nakajima Keiji , Kang Byung-Ho
Published: May 2023

Border-like cells (BLCs) are sheets of cells that are continuously sloughed off and replenished at the Arabidopsis root cap surface.ROOT CAP POLYGALACTURONASE (RCPG)encodes a putative pectinase involved in BLC shedding. Xylogalacturonan (XGA) is a pectic polysaccharide whose synthesis is associated with cell detachment and secreted separately from other cell wall polysaccharides.BEARSKIN1 (BRN1)andBRN2areArabidopsisNAC family transcription factors, andRCPGexpression is inhibited inbrn1/2. To explore the link between XGA and RCPG, we examined XGA synthesis inArabidopsislines with altered RCPG levels. We found that RCPG was contained in XGA-carrying vesicles budding from thetrans-Golgi, but XGA synthesis was not affected in thercpgmutant. XGA was absent in BLCs ofbrn2, but not ofbrn1, indicating thatBRN2is necessary for XGA synthesis. Overexpression of functional RCPG-GFP (oeRCPG-GFP) caused upregulation ofBRN2, ectopic XGA synthesis, overaccumulation of endogenous RCPG, and accelerated BLC turnover, suggesting a positive regulatory loop between RCPG and BRN2. Inactivation ofBRN2inoeRCPG-GFPsuppressed RCPG-GFP expression, excess RCPG, and XGA synthesis. Our data provide evidence that XGA and RCPG are secreted together and that BRN2 controls XGA synthesis, which facilitates RCPG export and BLC separation.
Staining and resin embedding of wholeDaphniamagna samples for micro-CT imaging enabling 3D visualization of cells, tissues, and organs of various thicknesses
Authors: Ngu Mee S. , Vanselow Daniel J. , Saint-Fort Rachelle A. , Sugarman Andrew L. , Zaino Carolyn R. , Yakovlev Maksim A. , Cheng Keith C. , Ang Khai C.
Published: May 2023

Micro-CT imaging is a powerful tool for generating high resolution, isotropic three-dimensional datasets of whole, centimeter-scale model organisms that can be used for qualitative and quantitative analysis. The small size, global freshwater distribution, wide range of cell size and structures of micron scale, and common use ofD. magnain toxicological and environmental studies make it an ideal model for demonstrating the potential power of micro-CT-enabled whole-organism phenotyping. This protocol details the steps involved inD. magnasamples preparation for micro-CT: euthanasia, fixation, staining, and resin embedding. Micro-CT reconstructions of samples imaged using synchrotron micro-CT reveal histological (microanatomic) features of organ systems, tissues, and cells in the context of the entire organism at sub-micron resolution, and in 3 dimensionality. The enabled “3D histology” and 3D renderings can be used towards morphometric analyses across cells, tissues, and organ systems for both descriptive and hypothesis testing studies.
Signatures of heuristic-based directed exploration in two-step sequential decision task behaviour
Authors: Brands A. M. , Mathar D. , Peters J.
Published: May 2023

Processes formalized in classic Reinforcement Learning (RL) theory, such as model-based (MB) control and exploration strategies have proven fertile in cognitive and computational neuroscience, as well as computational psychiatry. Dysregulations in MB control and exploration and their neurocomputational underpinnings play a key role across several psychiatric disorders. Yet, computational accounts mostly study these processes in isolation. The current study extended standard hybrid models of a widely-used sequential RL-task (two-step task; TST) employed to measure MB control. We implemented and compared different computational model extensions for this task to quantify potential exploration mechanisms. In two independent data sets spanning two different variants of the task, an extension of a classical hybrid RL model with a heuristic-based exploration mechanism provided the best fit, and revealed a robust positive effect of directed exploration on choice probabilities in stage one of the task. Posterior predictive checks further showed that the extended model reproduced choice patterns present in both data sets. Results are discussed with respect to implications for computational psychiatry and the search for neurocognitive endophenotypes.
Rescue of proteotoxic stress and neurodegeneration by the Zn2+transporter ZIP7
Authors: Guo Xiaoran , Mutch Morgan , Torres Alba Yurani , Nano Maddalena , McDonald Drew , Chen Zijing , Montell Craig , Dai Wei , Montell Denise J.
Published: May 2023

Proteotoxic stress drives numerous degenerative diseases. In response to misfolded proteins, cells adapt by activating the unfolded protein response (UPR), including endoplasmic reticulum-associated protein degradation (ERAD). However persistent stress triggers apoptosis. Enhancing ERAD is a promising therapeutic approach for protein misfolding diseases. From plants to humans, loss of the Zn2+transporter ZIP7 causes ER stress, however the mechanism is unknown. Here we show that ZIP7 enhances ERAD and that cytosolic Zn2+is limiting for deubiquitination of client proteins by the Rpn11 Zn2+metalloproteinase as they enter the proteasome in Drosophila and human cells. ZIP7 overexpression rescues defective vision caused by misfolded rhodopsin in Drosophila. Thus ZIP7 overexpression may prevent diseases caused by proteotoxic stress, and existing ZIP inhibitors may be effective against proteasome-dependent cancers.

One-Sentence Summary

Zn2+transport from the ER to the cytosol promotes deubiquitination and proteasomal degradation of misfolded proteins and prevents blindness in a fly neurodegeneration model.
Higher-order assembly is a regulatory switch that promotes outer kinetochore recruitment
Authors: Sissoko Gunter B. , Tarasovetc Ekaterina V. , Grishchuk Ekaterina L. , Cheeseman Iain M.
Published: May 2023

To faithfully segregate chromosomes during vertebrate mitosis, kinetochore-microtubule interactions must be restricted to a single site on each chromosome. Prior work on pair-wise kinetochore protein interactions has been unable to identify the mechanisms that prevent kinetochore formation in regions with a low density of CENP-A nucleosomes. To investigate the impact of higher-order assembly on kinetochore formation, we generated defined oligomers of the inner kinetochore protein CENP-T using two distinct, genetically engineered systems in human cells. Although individual CENP-T molecules interact poorly with other kinetochore proteins, oligomers that mimic the centromeric density of CENP-T trigger the robust formation of functional, cytoplasmic kinetochore-like particles. Both in cells andin vitro, each molecule of oligomerized CENP-T recruits substantially higher levels of outer kinetochore components than monomeric CENP-T molecules. Thus, the density-dependence of CENP-T restricts outer kinetochore recruitment to centromeres, where densely packed CENP-A recruits a high local concentration of CENP-T.
One particle per residue is sufficient to describe all-atom protein structures
Authors: Heo Lim , Feig Michael
Published: May 2023

Atomistic resolution is considered the standard for high-resolution biomolecular structures, but coarse-grained models are often necessary to reflect limited experimental resolution or to achieve feasibility in computational studies. It is generally assumed that reduced representations involve a loss of detail, accuracy, and transferability. This study explores the use of advanced machine-learning networks to learn from known structures of proteins how to reconstruct atomistic models from reduced representations to assess how much information is lost when the vast knowledge about protein structures is taken into account. The main finding is that highly accurate and stereochemically realistic all-atom structures can be recovered with minimal loss of information from just a single bead per amino acid residue, especially when placed at the side chain center of mass. High-accuracy reconstructions with better than 1 Å heavy atom root-mean square deviations are still possible when only Cα coordinates are used as input. This suggests that lower-resolution representations are essentially sufficient to represent protein structures when combined with a machine-learning framework that encodes knowledge from known structures. Practical applications of this high-accuracy reconstruction scheme are illustrated for adding atomistic detail to low-resolution structures from experiment or coarse-grained models generated from computational modeling. Moreover, a rapid, deterministic all-atom reconstruction scheme allows the implementation of an efficient multi-scale framework. As a demonstration, the rapid refinement of accurate models against cryoEM densities is shown where sampling at the coarse-grained level is guided by map correlation functions applied at the atomistic level. With this approach, the accuracy of standard all-atom simulation based refinement schemes can be matched at a fraction of the computational cost.

STATEMENT OF SIGNIFICANCE

The fundamental insight of this work is that atomistic detail of proteins can be recovered with minimal loss of information from highly reduced representations with just a single bead per amino acid residue. This is possible by encoding the existing knowledge about protein structures in a machine-learning model. This suggests that it is not strictly necessary to resolve structures in atomistic detail in experiments, computational modeling, or the generation of protein conformations via neural networks since atomistic details can inferred quickly via the neural network. This increases the relevance of experimental structures obtained at lower resolutions and broadens the impact of coarse-grained modeling.
Decryption of sequence, structure, and functional features of SINE repeat elements in SINEUP non-coding RNA–mediated post-transcriptional gene regulation
Authors: Sharma Harshita , Valentine Matthew N Z , Toki Naoko , Nishiyori Hiromi Sueki , Gustincich Stefano , Takahashi Hazuki , Carninci Piero
Published: May 2023

RNA structure folding largely influences RNA regulation by providing flexibility and functional diversity. In silico and in vitro analyses are limited in their ability to capture the intricate relationships between dynamic RNA structure and RNA functional diversity present in the cell. Here, we investigate sequence, structure and functional features of mouse and human SINE-transcribed retrotransposons embedded in SINEUPs long non-coding RNAs, which positively regulate target gene expression post-transcriptionally. In-cell secondary structure probing reveals that functional SINEs-derived RNAs contain conserved short structure motifs essential for SINEUP-induced translation enhancement. We show that SINE RNA structure dynamically changes between the nucleus and cytoplasm and is associated with compartment-specific binding to RBP and related functions. Moreover, RNA–RNA interaction analysis shows that the SINE-derived RNAs interact directly with ribosomal RNAs, suggesting a mechanism of translation regulation. We further predict the architecture of 18 SINE RNAs in three dimensions guided by experimental secondary structure data. Overall, we demonstrate that the conservation of short key features involved in interactions with RBPs and ribosomal RNA drives the convergent function of evolutionarily distant SINE-transcribed RNAs.
Periodic hypothalamic attractor-like dynamics during the estrus cycle
Authors: Liu Mengyu , Nair Aditya , Linderman Scott W. , Anderson David J.
Published: May 2023

Cyclic changes in hormonal state are well-known to regulate mating behavior during the female reproductive cycle, but whether and how these changes affect the dynamics of neural activity in the female brain is largely unknown. The ventromedial hypothalamus, ventro-lateral subdivision (VMHvl) contains a subpopulation of VMHvlEsr1+,Npy2r-neurons that controls female sexual receptivity. Longitudinal single cell calcium imaging of these neurons across the estrus cycle revealed that overlapping but distinct subpopulations were active during proestrus (mating-accepting) vs. non-proestrus (rejecting) phases. Dynamical systems analysis of imaging data from proestrus females uncovered a dimension with slow ramping activity, which generated approximate line attractor-like dynamics in neural state space. During mating, the neural population vector progressed along this attractor as male mounting and intromission proceeded. Attractor-like dynamics disappeared in non-proestrus states and reappeared following re-entry into proestrus. They were also absent in ovariectomized females but were restored by hormone priming. These observations reveal that hypothalamic line attractor-like dynamics are associated with female sexual receptivity and can be reversibly regulated by sex hormones, demonstrating that attractor dynamics can be flexibly modulated by physiological state. They also suggest a potential mechanism for the neural encoding of female sexual arousal.
Discovery of the apiosyltransferase, celery UGT94AX1 that catalyzes the biosynthesis of a flavone glycoside, apiin
Authors: Yamashita Maho , Fujimori Tae , An Song , Iguchi Sho , Takenaka Yuto , Kajiura Hiroyuki , Yoshizawa Takuya , Matsumura Hiroyoshi , Kobayashi Masaru , Ono Eiichiro , Ishimizu Takeshi
Published: May 2023

Apiose is a unique branched-chain pentose found in plant glycosides and a key component of the cell wall-polysaccharide pectin and other specialized metabolites. More than 1,200 plant-specialized metabolites contain apiose residues, represented by apiin, a distinctive flavone glycoside found in celery and parsley in the family Apiaceae. The physiological functions of apiin remain obscure, partly due to our lack of knowledge on apiosyltransferase during apiin biosynthesis. Here, we identified celery UGT94AX1 (AgApiT) as a novel apiosyltransferase, responsible for catalyzing the last sugar-modification step in apiin biosynthesis. AgApiT showed strict substrate specificity for the sugar donor, UDP-apiose, and moderate specificity for acceptor substrates, thereby producing various apiose-containing flavone glycosides in celery. Homology modeling of AgApiT with UDP-apiose, followed by site-directed mutagenesis experiments, identified unique Ile139, Phe140, and Leu356 residues in AgApiT, which are seemingly crucial for the recognition of UDP-apiose in the sugar donor pocket. Sequence comparison and molecular phylogenetic analysis of celery glycosyltransferases paralogous to AgApiT suggested thatAgApiTis the sole apiosyltransferase-encoding gene in the celery genome. This is the first report on the identification of a plant apiosyltransferase gene that will enhance our understanding of the physio-ecological functions of apiose and apiose-containing compounds.
Ventral pallidum projections to the ventral tegmental area reinforce but do not invigorate reward-seeking behavior
Authors: Palmer Dakota , Cayton Christelle A. , Scott Alexandra , Lin Iris , Newell Bailey , Weberg Morgan , Richard Jocelyn M.
Published: May 2023

Reward-predictive cues acquire motivating and reinforcing properties that contribute to the escalation and relapse of drug use in addiction. The ventral pallidum (VP) and ventral tegmental area (VTA) are two key nodes in brain reward circuitry implicated in addiction and necessary for the performance of cue-driven behavior. Evidence suggests that VP neurons projecting to the VTA (VP→VTA) promote cue-induced reinstatement of drug-seeking, but the mechanisms by which these neurons do so are undefined. In addition, the role of these neurons in the pursuit of non-drug reward is not known. In the current study, we usedin vivofiber photometry and optogenetics to record from and manipulate VP→VTA in rats performing a discriminative stimulus task (DS task) with sucrose reward to determine the fundamental role these neurons play in invigoration and reinforcement by reward and associated discriminative cues. We find that VP→VTA neurons are selectively active during reward consumption, that optogenetic stimulation of these neurons paired with reward consumption biases choice, and that VP→VTA optogenetic stimulation is reinforcing. Critically, we found no significant encoding of cue-elicited reward-seeking vigor and acute optogenetic stimulation of these neurons paired with cue onset did not enhance the probability or vigor of reward-seeking. Our results suggest that VP→VTA neurons are active during the consumption of natural reward and that this activity reinforces seeking behavior.
Changes in Active Site Loop Conformation Relate to the Transition toward a Novel Enzymatic Activity
Authors: Jacquet Pauline , Billot Raphaël , Shimon Amir , Hoekstra Nathan , Bergonzi Céline , Jenks Anthony , Chabrière Eric , Daudé David , Elias Mikael H.
Published: May 2023

Enzymatic promiscuity, the ability of enzymes to catalyze multiple, distinct chemical reactions, has been well documented and is hypothesized to be a major driver for the emergence of new enzymatic functions. Yet, the molecular mechanisms involved in the transition from one activity to another remain debated and elusive. Here, we evaluated the redesign of the active site binding cleft of the lactonaseSsoPox using structure-based design and combinatorial libraries. We created variants with largely improved catalytic abilities against phosphotriesters, the best ones being > 1,000-fold better compared to the wild-type enzyme. The observed shifts in activity specificity are large, ∼1,000,000-fold and beyond, since some variants completely lost their initial activity. The selected combinations of mutations have considerably reshaped the active site cavityviaside chain changes but mostly through large rearrangements of the active site loops, as revealed by a suite of crystal structures. This suggests that specific active site loop configuration is critical to the lactonase activity. Interestingly, analysis of high-resolution structures hints at the potential role of conformational sampling and its directionality in defining an enzyme activity profile.
A power law of cortical adaptation
Authors: Tring Elaine , Dipoppa Mario , Ringach Dario L.
Published: May 2023

How do neural populations adapt to the time-varying statistics of sensory input? To investigate, we measured the activity of neurons in primary visual cortex adapted to different environments, each associated with a distinct probability distribution over a stimulus set. Within each environment, a stimulus sequence was generated by independently sampling form its distribution. We find that two properties of adaptation capture how the population responses to a given stimulus, viewed as vectors, are linked across environments. First, the ratio between the response magnitudes is a power law of the ratio between the stimulus probabilities. Second, the response directions are largely invariant. These rules can be used to predict how cortical populations adapt to novel, sensory environments. Finally, we show how the power law enables the cortex to preferentially signal unexpected stimuli and to adjust the metabolic cost of its sensory representation to the entropy of the environment.
Tb2–x
Nd
x
Zn17–y
Ni
y
(x = 0.5, y = 4.83): a new intermetallic with a maximum disordered structure and its hydrogen storage properties
Authors: Nytka Vitalii , Kordan Vasyl , Stetskiv Andrij , Pavlyuk Volodymyr
Published: May 2023

The ternary Tb2–x
Nd
x
Zn17–y
Ni
y
(x = 0.5, y = 4.83) disordered phase belongs to the structural family based on the rhombohedral Th2Zn17 structure type. The structure is maximally disordered since all the sites are occupied by statistical mixtures of atoms. The Tb/Nd mixture of atoms occupies the 6c site (site symmetry 3m). The statistical mixtures Ni/Zn consisting of more Ni atoms are located in the 6c and 9d (symmetry .2/m) sites. In the following 18f (site symmetry .2) and 18h (site symmetry .m) sites are located Zn/Ni statistical mixtures which consist of more Zn atoms. Zn/Ni atoms form three-dimensional networks with hexagonal channels that fill statistical mixtures of Tb/Nd and Ni/Zn. The Tb2–x
Nd
x
Zn17–y
Ni
y
compound belongs to the family of intermetallic phases capable of absorbing hydrogen. In the structure, there are three types of voids, namely, 9e (site symmetry .2/m), 3b (site symmetry \overline{3}m) and 36i (site symmetry 1), in which hydrogen can be inserted, and the maximum total absorption capacity can reach 1.21 wt% H2. Electrochemical hydrogenation shows that the phase absorbs 1.03% of H2, which indicates partial filling of the voids with H atoms.
Crystal structure of a putative 3-hydroxypimelyl-CoA dehydrogenase, Hcd1, from Syntrophus aciditrophicus strain SB at 1.78 Å resolution
Authors: Dinh David M. , Thomas Leonard M. , Karr Elizabeth A.
Published: May 2023

Syntrophus aciditrophicus strain SB is a model syntroph that degrades benzoate and alicyclic acids. The structure of a putative 3-hydroxypimelyl-CoA dehydrogenase from S. aciditrophicus strain SB (SaHcd1) was resolved at 1.78 Å resolution. SaHcd1 contains sequence motifs and structural features that belong to the short-chain dehydrogenase/reductase (SDR) family of NADPH-dependent oxidoreductases. SaHcd1 is proposed to concomitantly reduce NAD+ or NADP+ to NADH or NADPH, respectively, while converting 3-hydroxypimelyl-CoA to 3-oxopimeyl-CoA. Further enzymatic studies are needed to confirm the function of SaHcd1.
Digitalisation and digital transformation in the social economy: the cases of Anecoop and Consum
Authors: Ribeiro-Navarrete Belén , Calderon-Monge Esther , Simón-Moya Virginia
Published: May 2023

Purpose

Digital technologies are changing the business landscape and the way companies are run. This research examines the implementation of digitalisation and digital transformation (DT) and explores the associated advantages and disadvantages.

Design/methodology/approach

Case study methodology was employed to help develop an understanding of how key actors implement DT. Semi-structured qualitative interviews were performed with managers of two social economy enterprises in the agri-food sector supply chain.

Findings

The specific nature of the supply chain of companies in this sector can hinder the implementation of certain digital technologies. This scenario results in two different approaches to digital technologies: one focused on digitalisation, and another focused on DT. Companies in this sector that seek successful implementation of DT should choose and combine appropriate digital technologies that fit with their DT strategy. They should also structure their organisation to ensure the leadership of senior management to engage all staff.

Originality/value

This study is valuable because of its focus on cooperatives in its analysis of DT. There is scant research on this business model, so the present study helps fill this gap in the literature.
Flow behavior and aerodynamic noise characteristics of ultra-high-speed elevator based on large eddy simulation
Authors: Zhang Xu , Jing Hao , Zhang Qing , Zhang Ruijun , Liu Lixin
Published: May 2023

Purpose

This paper aims to guide the implementation of noise reduction measures in hoistway and reduce the aerodynamic noise generated by elevator operation, this paper aims to propose an aerodynamic noise analysis method that can solve the flow field in hoistway.

Design/methodology/approach

A turbulence-acoustic model solving the flow field in a hoistway and a numerical wind hoistway model of the ultra-high-speed elevator were established by using large eddy simulation (LES) and Curle acoustic theory.

Findings

The characteristics of pulsating flow field and aerodynamic noise around ultra-high-speed elevator are analyzed. The asymmetric characteristics of the flow field could be observed using the turbulent kinetic energy and the instantaneous vortexes in the wind hoistway model. Vortex shedding, air flow separation and recombination around the car were the key factors for aerodynamic noise generation. The sound pressure level was approximately linear to the logarithm of car speed. The increase of car deflection angle in a certain range would reduce the peak frequency of wake noise and increase the sound pressure level (SPL) value.

Originality/value

This paper provides important guidance for researches studying the aerodynamic noise in the hoistway and the technical personnel that look for the reduction measures, which greatly improves the shortcomings in the numerical simulation of the aerodynamic noise of the hoistway.
Property level flood risk adaptation: technical and socioeconomic dimensions to resilience
Authors: Amadi Alolote
Published: May 2023

Purpose

Understanding the technical and socioeconomic dimensions to resilience is core to making a business case for property-level flood risk adaptation. The study investigates the socioeconomic factors that impact the technical dimensions to property-level flood risk adaptation, and whether there is a typology of households adopting similar adaptation measures in Port Harcourt.

Design/methodology/approach

Exploratory and inferential statistical analysis of data collated from 407 questionnaires was carried out. Using chi-square analysis, significant bivariate associations were sought between the level of uptake of different categories of property level adaptation and the socioeconomic characteristics of households. A two-step cluster analysis was used to explore discernible patterns of households implementing similar adaptation measures. Logistic regression analysis was further used to evaluate the extent to which socioeconomic parameters impact residents' willingness to undertake adaptation measures given the option of relocation.

Findings

The chi-square analysis highlighted a lack of significant association between some socioeconomic parameters and the uptake of individual adaptation measures. The regression analysis however showed that the socioeconomic parameters exert varying degrees of influence on the residents' willingness to undertake adaptation measures. Two homogeneous groups of residents with similar socioeconomic characteristics were identified via the cluster analysis but did not translate into strongly discernible adaptation differences/patterns.

Practical implications

The study shows that although socioeconomic parameters to some extent underlie the technical dimensions to flood resilience, there is no distinctive typology of households in Port Harcourt adopting a similar combination of measures.

Originality/value

The study offers insights into understanding property-level flood risk adaptation responses within the context of the developing world.
Examining the impact of top management support on employee creativity through the mediating role of knowledge management and absorptive capacity
Authors: Al-Husseini Sawasn
Published: May 2023

Purpose

Drawing on the knowledge-based view and social exchange theory, this study aims to examine how top management support relates both directly and indirectly to employee creativity through knowledge management processes (acquisition and sharing) and absorptive capacity.

Design/methodology/approach

Data were collected from 284 academics and researchers working in research centres in Iraq’s public universities to assess their perceptions of management support, knowledge management, absorptive capacity and creativity.

Findings

Performing structural equation modelling with AMOS, positive relationships were identified between top management support, knowledge management processes, absorptive capacity and employee creativity. The study findings emphasise the pivotal role of top management support in creating an environment that fosters knowledge acquisition and sharing, and enhancing absorptive capacity, in turn, amplifying employee creativity. Empirical evidence confirming the salient role of knowledge management and absorptive capacity in strengthening employee creativity in the context of Iraqi academia and researchers is presented.

Originality/value

The study shows that knowledge management processes and absorptive capacity mediate the influence of top management support on employee creativity. The premise of absorptive capacity is the individual’s ability to identify, accumulate and assimilate relevant knowledge from external sources and commercialise the gained knowledge.
Enabling supply chain efficacy through supply chain absorptive capacity and ambidexterity: empirical study from Middle East region - a moderated-mediation model
Authors: Alsmairat Mohammad A.K. , AL-Shboul Moh'd Anwer
Published: May 2023

Purpose

This study tries to examine how supply chain (SC) absorptive capacity (AC), SC ambidexterity, SC risk mitigation and supply chain agility (SCA) affect SC efficacy (SCE) in manufacturing firms (MFs) in the Middle East region.

Design/methodology/approach

Using a quantitative approach through a survey-based study, 1,004 questionnaires were distributed to the MFs that are listed in the chambers of the industries of Jordan, Egypt, Saudi Arabia and Bahrain in the Middle East region, with 239 useable and valid responses retrieved for analysis, representing a 23.8% response rate. The main respondents were chief executive managers, operations managers, managers and logistics managers from both mid and top levels. The conceptual model was tested by using a hypothesis-testing deductive approach. The findings are based on covariance-based analysis and structural equation modeling (SEM) using partial least squares-SEM (PLS-SEM) software.

Findings

This study illustrates a significant relationship between SC AC, SC ambidexterity, SC risk mitigation and SCA on SCE. Further, the findings indicate that there is a significant effect of SC risk mitigation as a mediating factor in the relationship between SC AC, and SC ambidexterity on SCE directly and indirectly, as well through a moderating effect of SCA in these relations. Finally, there is a significant direct and indirect effect of SCA in the relationship between SC AC and SC ambidexterity on SCE as a moderating factor.

Originality/value

This study presents theoretical and empirical insights that both SC risk mitigation and SCA are proper logistics features for mediating and moderating extends the literature by adding a positive role of SC AC and SC ambidextrousness in mitigating SC risks. However, this study adds up the SC literature by evidencing moderating role of SCA between the absorptive capacities, ambidexterity on SCE. Such findings of this study can provide insightful implications for managers and practitioners at different levels in and efficacy among MFs (MFs, stakeholders and policymakers regarding the importance of using the three mentioned enablers on SCE) in MFs, particularly in the Middle Eastern firms and in developing countries in general East region.
Unveiling the effect of benign and malicious envy toward social media influencers on brand choice
Authors: Wang Tien , Thai Trung Dam-Huy , Yeh Ralph Keng-Jung , Tamariz Fadic Camila
Published: May 2023

Purpose

Drawing from social comparison theory, this study investigates the factors influencing benign or malicious envy toward influencers and the effects of envy on social media users' choice of endorsed or rival brands.

Design/methodology/approach

A sample of 453 social media users was obtained to examine the research model.

Findings

Homophily and symbolism positively affect both benign and malicious envy. Credibility affects benign envy positively but malicious envy negatively. Deservingness affects malicious envy negatively but exerts no effect on benign envy. Benign envy has a greater influence on choosing brands endorsed by influencers than it does on choosing rival brands; these effects are more substantial under conditions of high perceived control. By contrast, malicious envy significantly affects the choice of purchasing rival brands; however, this effect is not influenced by perceived control.

Originality/value

This study unveils a key aspect of the endorser–follower relationship by analyzing the effect of envy toward social media influencers on followers' intention to purchase endorsed or rival brands. This study identifies the differential effects of two types of envy on brand choice.
Effective communication in BIM as a driver of CSR under the happiness management approach
Authors: Villena Manzanares Francisco , García-Segura Tatiana , Pellicer Eugenio
Published: May 2023

Purpose

Building information modeling (BIM) is a growing technology and methodology for project design in the construction industry. However, when the project design team designs with BIM in a free-form manner (without a qualified instructor), it is not clear how behavior or trust might develop among project team members, nor if there are variables that might influence the improvement of such collaboration.

Design/methodology/approach

A sample of 92 responses was obtained from managers of project design firms in the architecture, engineering and construction (AEC) sector. The questionnaire data were analyzed using partial least square structural equation modeling (PLS-SEM).

Findings

This paper provides an explanation, from a happiness management perspective, to reflect on the importance of establishing policies to enhance effective communication between project team members in BIM design, as it improves trust between team members and their collaborators, developing the overall satisfaction of all the agents involved in the project.

Originality/value

The researchers suggest that there is a gap in the literature on how effective communication influences the implementation of BIM methodology.