bluuebunny/crossref_metadata_2025 huggingface dataset:
Purified fibers in chemically defined synthetic diets destabilize the gut microbiome of an omnivorous insect model
Authors: Dockman Rachel L. , Ottesen Elizabeth A.
Published: May 2024

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The macronutrient composition of a host’s diet shapes its gut microbial community, with dietary fiber in particular escaping host digestion to serve as a potent carbon source for gut microbiota. Despite widespread recognition of fiber’s importance to microbiome health, nutritional research often fails to differentiate hyper-processed fibers from cell-matrix derived intrinsic fibers, limiting our understanding of how individual polysaccharides influence the gut community. We use the American cockroach (Periplaneta americana) as a model system to dissect the response of complex gut microbial communities to diet modifications that are impossible to test in traditional host models. Here, we designed synthetic diets from lab-grade, purified ingredients to identify how the cockroach microbiome responds to six different carbohydrates (chitin, methylcellulose, microcrystalline cellulose, pectin, starch, xylan) in otherwise balanced diets. We show via 16S rRNA gene profiling that these synthetic diets reduce bacterial diversity and alter the phylogenetic composition of cockroach gut microbiota in a fiber-dependent manner, regardless of the vitamin and protein content of the diet. Comparisons with cockroaches fed whole-food diets reveal that synthetic diets induce blooms in common cockroach-associated taxa and subsequently fragment previously stable microbial correlation networks. Our research leverages an unconventional microbiome model system and customizable lab-grade artificial diets to shed light on how purified polysaccharides, as opposed to nutritionally complex intrinsic fibers, exert substantial influence over a normally stable gut community.
Exploring Probiotic Potential: A Comparative Genomics and In Silico Assessment of Genes within the GenusGeobacillus
Authors: Najar Ishfaq Nabi , Sharma Prayatna , Das Rohit , Mondal Krishnendu , Singh Ashish Kumar , Radha Anu , Sharma Varsha , Sharma Sonali , Thakur Nagendra , Gandhi Sumit G. , Kumar Vinod
Published: May 2024

The pursuit of new probiotic targets has seen a surge, aided by next-generation sequencing, facilitating a thorough exploration of bacterial traits. The genusGeobacillusstands out as a promising target for uncovering its potential as a probiotic. The study explored the genetic attributes of the genusGeobacillusfor their resilience to gastrointestinal conditions, nutrient production, and immunomodulatory compound creation, revealing potential probiotic traits. Additionally, the research undertook predictive analyses of genomic elements such as prophages, CRISPR-Cas systems, insertion sequences, genomic islands, antibiotic resistance genes, and CAZymes. These evaluations aimed to assess the safety aspects associated with the genusGeobacillus. A comparative genomic analysis was also carried out using 18 validly published genomes of the genusGeobacillusand a few other genomes ofLactobacillusandBifidobacteriumwere taken as control. Genes associated with probiotic traits like adhesion, stress tolerance (acid/bile, osmotic, oxidative), immune modulation, and molecular chaperones were uniformly detected in theGeobacillusgenus. Notably, mobile genetic elements such as plasmids, prophages, and insertion sequences were absent, as were virulence factors, toxins, and Antibiotic resistance genes. Additionally, CRISPR-Cas systems and CAZymes were present. The pan-genome encompassed 25,284 protein-coding genes with translation. Comparative genomic analysis revealed an open pan-genome forGeobacillus. Pan-genome exhibited variability, particularly in genes linked to environmental interaction and secondary metabolite synthesis. In conclusion,Geobacillusappears potentially safe and well-suited for the gut habitat. However, furtherin vitrostudies are essential to add to the knowledge of the probiotic potential ofGeobacillusspecies.

Importance

This comprehensive study highlights the significant probiotic potential and genetic makeup of theGeobacillusgenus, shedding light on its unique attributes in adapting to extreme environmental conditions. Understanding the probiotic properties ofGeobacillusis crucial amidst growing concerns over antibiotic resistance, offering promising alternatives for combating pathogenic microbes. Additionally, exploring the genetic diversity and adaptive mechanisms ofGeobacillusthrough genomic and metagenomic approaches provides valuable insights into its biotechnological applications and evolutionary history. By employing in-silico methods and comparative analyses with established probiotic genera, this study contributes to elucidating the probiotic characteristics ofGeobacillus, paving the way for further research in harnessing its beneficial traits for various applications in health, biotechnology, and environmental remediation.
A duplexed CRISPRi-based approach to predict synergistic antibiotic targets inEscherichia coli
Authors: Xiong Xianyi , Furseth Hannah , McCoy Brady , Slavic Lauren , Yuan Xun , Chen Sydney , Baughn Anthony D. , Minato Yusuke , Harcombe William R.
Published: May 2024

Co-repressing drug targets with CRISPR interference (CRISPRi) has the potential to predict both synergistic and additive drug combinations. In a screen experiment withEscherichia coli, pairwise gene co-repression assays correctly predicted the interaction type observed for 36 antibiotic pairs in checkerboard assays. Furthermore, we used this approach to identify promising synergistic interactions with a gene currently not targeted by clinical antibiotics. CRISPRi can systematically test the impact of gene inhibitions and identify novel drug targets.
Expanding the cultivable human archaeome:Methanobrevibacter intestinisp. nov. and strainMethanobrevibacter smithii “GRAZ-2”from human feces
Authors: Weinberger Viktoria , Mohammadzadeh Rokhsareh , Blohs Marcus , Kalt Kerstin , Mahnert Alexander , Moser Sarah , Cecovini Marina , Mertelj Polona , Zurabishvili Tamara , Wolf Jacqueline , Shinde Tejus , Madl Tobias , Habisch Hansjörg , Kolb Dagmar , Pernitsch Dominique , Hingerl Kerstin , Metcalf William , Moissl-Eichinger Christine
Published: May 2024

Two mesophilic, hydrogenotrophic methanogens, WWM1085 andM. smithiiGRAZ-2 were isolated from human fecal samples. WWM1085 was isolated from an individual in the USA, and represents a novel species with in the genusMethanobrevibacter.M. smithiiGRAZ-2 (= DSM 116045) was retrieved from fecal samples of a European, healthy female and represents a novel strain within this genus. BothMethanobrevibacterrepresentatives form non-flagellated, short rods with variable morphologies and the capacity to form filaments. Both isolates showed the typical fluorescence of F420and methane production.

Compared toM. smithiiGRAZ-2, WWM1085 did not accumulate formate when grown on H2and CO2. The optimal growth conditions were at 37°C, and pH 7. Full genome sequencing revealed a genomic difference of WWM1085 to the type strain ofM. smithiiPS (type strain; DSM 861), with 93.55% ANI and major differences in the sequence of itsmcrAgene (3.3% difference in nucleotide sequence). Differences in the 16S rRNA gene were very minor and thus distinction based on this sequence might not be possible.M. smithiiGRAZ-2 was identified as a novel strain within theMethanobrevibactergenus (ANI 99.04 % toM. smithiiPS).

Due to the major differences of WWM1085 andM. smithiitype strain PS in phenotypic, genomic and metabolic features, we proposeM. intestinisp. nov. as a novel species with WWM1085 as the type strain (DSM 116060T = CECT 30992).
Genomic perspectives on foodborne illness
Authors: Lipman David J. , Cherry Joshua L. , Strain Errol , Agarwala Richa , Musser Steven M.
Published: May 2024

Whole-genome sequencing of bacterial pathogens is used by public health agencies to link cases of food poisoning caused by the same source of contamination. The vast majority of these appear to be sporadic cases associated with small contamination episodes and do not trigger investigations. We analyzed clusters of sequenced clinical isolates ofSalmonella,Escherichia coli,Campylobacter, andListeriathat differ by only a small number of mutations to provide a new understanding of the underlying contamination episodes. These analyses provide new evidence that the youngest age groups have greater susceptibility to infection fromSalmonella,Escherichia coli, andCampylobacterthan older age groups. This age bias is weaker for the commonSalmonellaserovar Enteritidis than Salmonella in general. Analysis of these clusters reveals significant regional variations in relative frequencies ofSalmonellaserovars across the United States. A large fraction of the contamination episodes causing sickness appear to have long duration. For example, 50% of theSalmonellacases are in clusters that persist for almost three years. For all four pathogen species, the majority of the cases were part of genetic clusters with illnesses in multiple states and likely to be caused by contaminated commercially distributed foods. The vast majority ofSalmonellacases among infants < 6 months of age appear to be caused by cross-contamination from foods consumed by older age groups or by environmental bacteria rather than infant formula contaminated at production sites.
Genomic loss of GPR108 disrupts AAV transduction in birds
Authors: Nevue Alexander A. , Sairavi Anusha , Huang Samuel J. , Nakai Hiroyuki , Mello Claudio V.
Published: May 2024

The G protein-coupled receptor 108 (GPR108) gene encodes a protein factor identified as critical for adeno-associated virus (AAV) entry into mammalian cells, but whether it is universally involved in AAV transduction is unknown. Remarkably, we have discovered thatGPR108is absent in the genomes of birds and in most other sauropsids, providing a likely explanation for the overall lower AAV transduction efficacy of common AAV serotypes in birds compared to mammals. Importantly, transgenic expression of humanGPR108and manipulation of related glycan binding sites in the viral capsid significantly boost AAV transduction in zebra finch cells. These findings contribute to a more in depth understanding of the mechanisms and evolution of AAV transduction, with potential implications for the design of efficient tools for gene manipulation in experimental animal models, and a range of gene therapy applications in humans.
Combining DNA and protein alignments to improve genome annotation with LiftOn
Authors: Chao Kuan-Hao , Heinz Jakob M. , Hoh Celine , Mao Alan , Shumate Alaina , Pertea Mihaela , Salzberg Steven L
Published: May 2024

As the number and variety of assembled genomes continues to grow, the number of annotated genomes is falling behind, particularly for eukaryotes. DNA-based mapping tools help to address this challenge, but they are only able to transfer annotation between closely-related species. Here we introduce LiftOn, a homology-based software tool that integrates DNA and protein alignments to enhance the accuracy of genome-scale annotation and to allow mapping between relatively distant species. LiftOn’s protein-centric algorithm considers both types of alignments, chooses optimal open reading frames, resolves overlapping gene loci, and finds additional gene copies where they exist. LiftOn can reliably transfer annotation between genomes representing members of the same species, as we demonstrate on human, mouse, honey bee, rice, andArabidopsis thaliana. It can further map annotation effectively across species pairs as far apart as mouse and rat orDrosophila melanogasterandD. erecta.
Using machine learning to dissect host kinases required forLeishmaniainternalization and development
Authors: Wei Ling , Barrie Umaru , Aloisio Gina M. , Khuong Francis T. H. , Arang Nadia , Datta Arani , Kaushansky Alexis , Wetzel Dawn M.
Published: May 2024

TheLeishmanialife cycle alternates between promastigotes, found in the sandfly, and amastigotes, found in mammals. When an infected sandfly bites a host, promastigotes are engulfed by phagocytes (i.e., neutrophils, dendritic cells, and macrophages) to establish infection. When these phagocytes die or break down, amastigotes must be re-internalized to survive within the acidic phagolysosome and establish disease. To define host kinase regulators ofLeishmaniapromastigote and amastigote uptake and survival within macrophages, we performed an image-based kinase regression screen using a panel of 38 kinase inhibitors with unique yet overlapping kinase targets. We also targeted inert beads to complement receptor 3 (CR3) or Fcγ receptors (FcR) as controls by coating them with complement/C3bi or IgG respectively. Through this approach, we identified several putative host kinases that regulate receptor-mediated phagocytosis and/or the uptake ofL. amazonensis. Findings included kinases previously implicated inLeishmaniauptake (such as Src family kinases (SFK), Abl family kinases (ABL1/c-Abl, ABL2/Arg), and spleen tyrosine kinase (SYK)), but we also uncovered many novel kinases. Our methods also predicted host kinases necessary for promastigotes to convert to amastigotes or for amastigotes to survive within macrophages. Overall, our results suggest that the concerted action of multiple interconnected networks of host kinases are needed over the course ofLeishmaniainfection, and that the kinases required for the parasite’s life cycle may differ substantially depending on which receptors are bound and the life cycle stage that is internalized. In addition, using our screen, we identified kinases that appear to preferentially regulate the uptake of parasites over beads, indicating that the methods required forLeishmaniato be internalized by macrophages may differ significantly from generalized phagocytic mechanisms. Our findings are intended to be used as a hypothesis generation resource for the broader scientific community studying the roles of kinases in host-pathogen interactions.
TMS-based neurofeedback training of mental finger individuation induces neuroplastic changes in the sensorimotor cortex
Authors: Odermatt Ingrid A , Schulthess-Lutz Manuel , Mihelj Ernest , Howell Paige , Heimhofer Caroline C , McMackin Roisin , Ruddy Kathy , Freund Patrick , Kikkert Sanne , Wenderoth Nicole
Published: May 2024

Neurofeedback (NF) training based on motor imagery is increasingly used in neurorehabilitation with the aim to improve motor functions. However, the neuroplastic changes underpinning these improvements are poorly understood. Here, we used mental finger individuation, i.e., the selective facilitation of single finger representations without producing overt movements, as a model to study neuroplasticity induced by NF. To enhance mental finger individuation, we used transcranial magnetic stimulation (TMS)-based NF training. During motor imagery of individual finger movements, healthy participants were provided visual feedback on the size of motor evoked potentials, reflecting their finger-specific corticospinal excitability. We found that TMS-NF improved the top-down activation of finger-specific representations. First, intracortical inhibitory circuits in the primary motor cortex were tuned after training such that inhibition was selectively reduced for the finger that was mentally activated. Second, motor imagery finger representations in sensorimotor areas assessed with functional MRI became more distinct after training. Together, our results indicate that the neural underpinnings of finger individuation, a well-known model system for neuroplasticity, can be modified using TMS-NF guided motor imagery training. These findings demonstrate that TMS-NF induces neuroplasticity in the sensorimotor system, highlighting the promise of TMS-NF on the recovery of fine motor function.
A neuroimaging dataset during sequential color qualia similarity judgments with and without reports
Authors: Hirao Takahiro , Miyamae Mitsuhiro , Matsuyoshi Daisuke , Inoue Ryuto , Takado Yuhei , Obata Takayuki , Higuchi Makoto , Tsuchiya Naotsugu , Yamada Makiko
Published: May 2024

Recent neuroscientific research has advanced our understanding of consciousness, yet the connection between specific qualitative aspects of consciousness, known as “qualia,” and particular brain regions or networks remains elusive. Traditional methods that rely on verbal descriptions from participants pose challenges in neuroimaging studies. To address this, our group has introduced a novel “qualia structure” paradigm that leverages exhaustive, structural, and relational comparisons among qualia instead of verbal reports. In this study, we present the first fMRI dataset that captures relational similarity judgments among two out of nine color qualia per trial from 35 participants. This dataset also includes a “no-report” condition in half of the trials to assess the impact of overt reporting. Additionally, each participant’s color discriminability was evaluated with a hue test conducted outside the scanner. Our data offer valuable insights into the brain functions associated with color qualia and contribute to a deeper understanding of the neural foundations of consciousness.
Self-cleaving ribozymes conserved in RNA viruses unveil a new role in protein translation
Authors: López-Galiano María José , Chiba Sotaro , Forgia Marco , Navarro Beatriz , Cervera Amelia , Babaian Artem , Di Serio Francesco , Turina Massimo , de la Peña Marcos
Published: May 2024

Small self-cleaving ribozymes are catalytic RNAs originally discovered in viroid-like agents, which are infectious circular RNAs (circRNAs) postulated as relics of a prebiotic RNA world. In the last decade, however, small ribozymes have also been detected across the tree of life, from bacterial to human genomes, and more recently, in viral agents with circRNA genomes. Here we report the conserved occurrence of small ribozymes within the linear genomes of typical ds and ssRNA viruses from fungi and plants. In most 5’-UTR regions of chrysovirids and fusarivirids, we find conserved type I hammerhead ribozymes (hhrbzs) showing efficient self-cleaving activityin vitroandin vivo. Similar hhrbzs, as well as hepatitis delta and twister ribozymes, were also detected in megabirna-, hypo-, fusagra- and toti-like viruses. These ribozymes occur as isolated motifs but also as close tandem pairs, suggesting that they are involved in the formation of ∼300 nt circRNAs.In vivocharacterization of a chrysovirid hhrbz revealed its unexpected role in protein translation as an internal ribosome entry site (IRES). RNA structural comparison between the hammerhead three-way junction and the core domain of picornavirus IRES elements allow us to suggest that these simple ribozymes may follow a similar strategy to achieve cap-independent translation. We conclude that self-cleaving ribozymes, historically involved in the rolling circle replication of viroid-like agents, have been exapted towards translational functions in linear RNA viruses.
Reconciling Flexibility and Efficiency: Medial Entorhinal Cortex Represents a Compositional Cognitive Map
Authors: Piray Payam , Daw Nathaniel D
Published: May 2024

The influential concept of a cognitive map envisions that the brain builds mental representations of objects, barriers, and goals. This idea has been formalized in a range of computational models that show how such representations can be useful for guiding goal-directed behavior, for instance by planning novel routes to maximize long-run rewards. One key feature of flexible cognitive representations generally is that they exploit compositionality – the ability to build complex structures by recombining simpler parts. However, how this principle plays out in neural representations of cognitive maps and map-based planning remains largely unexplored. Indeed, as we show here, compositionality can be difficult to reconcile with efficient planning: because reuse tends to oppose flexibility, it is challenging to construct a compositional representation of the environment which is also organized in a way that enables generalizability and efficient planning. Here, we propose a novel model for efficiently creating and planning with compositional predictive maps, and further show that it successfully simulates various aspects of response fields in the medial entorhinal cortex, particularly object vector cells and grid cells. The model treats each object as an alteration to a baseline map linked to open space, creating complete predictive maps by combining object-related representations compositionally. Overall, this work provides a comprehensive and realistic model for efficient model learning and model-based planning in animals, and offers insights into the brain processes supporting efficient, flexible planning using compositional predictive maps.
Comparative Analysis of the Techniques for the Determination of Binding Affinity between a Small Molecule Inhibitor and a Protein Target
Authors: Luo Yalan , Chen Yijun
Published: May 2024

The binding affinity constant (KD) between a small molecule inhibitor and a protein target is pivotal parameter for target identification and early drug discovery. Despite the extensive applications of three major techniques, namely SPR, ITC and MST, theKDvalues for a specifically defined binding measured by these techniques are drastically different, which poses a remarkable difficulty to deal with these ambiguous data. Here, we report the evaluation of the accuracy ofKDvalues from SPR, ITC and MST compared with enzyme kinetics. To enable an objective comparison, we theoretically proved that enzyme competitive inhibition constant (Ki) could directly reflect the binding affinity. Using purine nucleoside phosphorylase, its substrate inosine and competitive inhibitor immucillin-H, we determined respectiveKDandKivalues to make a direct comparison. Moreover, we found that theKDvalue measured by SPR is more relevant to itsKivalue. This study highlights the urgent need on the development of new technologies for the determination of binding affinity between small molecule inhibitors and protein targets.
Biological activities and metabolic profile of endophyticBacillus haynesiifromMomordica charantia
Authors: Sharma Garima , Agarwal Surbhi , Bhardwaj Rashmi , Barvkar Vitthal T. , Kumar Vinay , Mathur Vartika
Published: May 2024

Endophytes share a complex intimate relationship due to which they are capable of synthesizing metabolites that are either similar or derivative of host bioactive compounds. Such endophytes especially from medicinal plants can be prospected for commercial-scale production of the therapeutic compound. Thus, the study evaluates the antioxidant and anti-inflammatory potential ofMomordica charantiafruit endophyteBacillus haynesiiR2MCFF61, and determines its metabolite profile through LC-Q-TOF-MS for the bioactive compounds produced.B. haynesiiR2MCFF61 showed significant antioxidant and anti-inflammatory potential with increased DPPH scavenging activity in the standard compound and inhibition of protein denaturation respectively. The metabolic profile of this endophyte showed 23 compounds, mostly consisting of metabolites from lipid, phenylpropanoid and triterpenoid pathways.B. haynesiiR2MCFF61 showed production of cucurbitane-triterpenoids namely Momordicoside K, 19-dimethoxycucurbita-5(10),6,22(E),24-tetraen-3β-ol and 23(E)-7β-methoxycucurbita-5,23,25-trien-3β-ol. These compounds are mainly produced byM. charantiafruit and their production by its endophyte is reported for the first time. Thus, these results indicate the promising therapeutic potential ofB. haynesiiR2MCFF61 which can be utilized as a low-cost sustainable source of these bioactive compounds.
A phosphate-binding pocket in cyclin B3 is essential for XErp1/ Emi2 degradation in meiosis I
Authors: Demmig Rebecca , Schäfer Michael , Johannes Elijah , Heim Andreas , Boland Andreas , Mayer Thomas U.
Published: May 2024

To ensure the correct euploid state of embryos, it is essential that vertebrate oocytes await fertilization arrested at metaphase of meiosis II. This MII arrest is mediated by XErp1/Emi2, which inhibits the ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome). Cyclin B3 in complex with Cdk1 (cyclin-dependent kinase 1) is essential to prevent an untimely arrest of vertebrate oocytes in meiosis I by targeting XErp1/Emi2 for degradation. Yet, the molecular mechanism of XErp1/Emi2 degradation in MI is not well understood. Here, by combining TRIM-Away in oocytes with egg extract andin vitrostudies, we demonstrate that a hitherto unknown phosphate-binding pocket in cyclin B3 is essential for efficient XErp1/Emi2 degradation in meiosis I. This pocket enables Cdk1/cyclin B3 to bind pre-phosphorylated XErp1/Emi2 facilitating further phosphorylation events, which ultimately target XErp1/Emi2 for degradation in a Plk1 (Polo-like kinase 1) dependent manner. Key elements of this degradative mechanism are conserved in frog and mouse. Our studies identify a novel, evolutionarily conserved determinant of Cdk/cyclin substrate specificity essential to prevent an untimely oocyte arrest at meiosis I with catastrophic consequences upon fertilization.
SLAMseq reveals transfer of RNA from liver to kidney in the mouse
Authors: Hunter Robert W , Sun Jialin , Palmer Trecia , Bailey Matthew A , Dhaun Neeraj , Buck Amy , Dear James W
Published: May 2024

Extracellular RNA (exRNA) mediates intercellular communication in plants and lower animals; whether it serves a signalling function in mammals is controversial. Reductionist experiments, in which a single RNA is over-expressed or tagged, have shown RNA transfer between tissues but these may not be relevant to normal physiology. For example, the microRNA miR-122 is released from injured hepatocytes and is taken up by kidney cells. We sought to determine the scale of RNA transfer between liver and kidney through the metabolic labelling of RNA in mice. We used 4-thiouracil to specifically label RNA in hepatocytes then detected labelled (thiolated) RNA in the kidney using SLAMseq: SH-Linked Alkylation for the Metabolic sequencing of RNA. In the kidney, mRNA labelling was detected in 5% of all kidney transcripts under healthy conditions and was increased to 34% of kidney transcripts after acute hepatocellular injury. Labelling was evident in kidney transcripts mapping to known hepatocyte marker genes, to a greater extent than those mapping to markers of other cell types. Labelled small RNA was not detected in kidney tissue. Our results are consistent with the transfer of RNA from liver to kidney; this transfer is augmented in liver injury.
Deep dive into the diversity and properties of rhodopsins in actinomycetes of the familyGeodermatophilaceae
Authors: Tarlachkov Sergey V. , Starodumova Irina P. , Boueva Olga V. , Chernyshov Sergei V. , Evtushenko Lyudmila I.
Published: May 2024

Rhodopsin with the NTQ motif and heliorhodopsins, both discovered for the first time in actinomycetes of the familyGeodermatophilaceaewere characterized, along with characterization of the DTEW, DTEF and NDQ rhodopsins reported in members of this family previously. The identified absorption maxima ranged from 513 to 559 nm, of which the blue-shifted rhodopsin contained the NTQ motif and the red-shifted one were heliorhodopsin. An assessment of the pumping activity of the NTQ rhodopsin and heliorhodopsin showed that the former functioned as inward Cl--, Br--, I--pump with much weaker activity towards NO3-, while no any activity was detected for the later. The DTEW and DTEF rhodopsins had the outward H+-transport activity which was dependent on the presence of Ca2+ions and on the particularE. coliexpression strain. The outward pumping of H+was also detected for NDQ rhodopsin both in NaCl and KCl solutions at pH 5 and 6, but not at pH 7. Weak Na+-efflux activity for this rhodopsin was observed at pH 6 and 7 in NaCl solution only after adding carbonyl cyanide m-chlorophenyl hydrazone (CCCP).
Development and Characterization of Recombinant ADP-Ribose Binding Reagents that Allow Simultaneous Detection of Mono and Poly ADP-Ribose
Authors: Chiu Shu-Ping , Camacho Cristel V. , Kraus W. Lee
Published: May 2024

ADP-ribosylation (ADPRylation) is a post-translational modification (PTM) of proteins mediated by the activity of a variety of ADP-ribosyltransferase (ART) enzymes, such as the Poly (ADP-ribose) Polymerase (PARP) family of proteins. This PTM is diverse in both form and biological functions, which makes it a highly interesting modification, but difficult to study due to limitations in reagents available to detect the diversity of ADP-ribosylation. Recently we developed a set of recombinant antibody-like ADP-ribose binding proteins, using naturally occurring ADPR binding domains (ARBDs) that include macrodomains and WWE domains, that have been functionalized by fusion to the constant “Fc” region of rabbit immunoglobulin. Herein, we present an expansion of this biological toolkit, where we have replaced the rabbit Fc sequence with two other species, the Fc for mouse and goat immunogloblulin. Characterization of the new reagents indicates that they can be detected in a species-dependent manner, recognize specific ADP-ribose moieties, and excitingly, can be used in various antibody-based assays by co-staining. The expansion of this tool will allow for more multiplexed assessments of the complexity of ADPRylation biology in many biological systems.
Molecular basis for the host range function of the poxvirus PKR inhibitor E3
Authors: Haller Sherry L. , Park Chorong , Bruneau Ryan C , Megawati Dewi , Zhang Chi , Vipat Sameera , Peng Chen , Senkevich Tatiana G. , Brennan Greg , Tazi Loubna , Rothenburg Stefan
Published: May 2024

The antiviral protein kinase R (PKR) is activated by viral double-stranded RNA and phosphorylates translation initiation factor eIF2α, thereby inhibiting translation and virus replication. Most poxviruses contain two PKR inhibitors, called E3 and K3 in vaccinia virus (VACV), which are determinants of viral host range. The prevailing model for E3 function is that it inhibits PKR through the non-specific sequestration of double-stranded (ds) RNA. Our data revealed that Syrian hamster PKR was resistant to E3, which is at odds with the sequestration model. However, Syrian hamster PKR was still sensitive to K3 inhibition. In contrast, Armenian hamster PKR showed opposite sensitivities, being sensitive to E3 and resistant to K3 inhibition. Mutational analyses of hamster PKRs showed that sensitivity to E3 inhibition was largely determined by the region linking the dsRNA-binding domains and the kinase domain of PKR, whereas two amino acid residues in the kinase domain (helix αG) determined sensitivity to K3. Expression of PKRs in congenic cells showed that Syrian hamster PKR containing the two Armenian hamster PKR residues in helix-αG was resistant to wild type VACV infection, and that cells expressing either hamster PKR recapitulated the phenotypes observed in species-derived cell lines. The observed resistance of Syrian hamster PKR to E3 explains its host range function and challenges the paradigm that dsRNA-binding PKR inhibitors mainly act by the sequestration of dsRNA.

Significance

The molecular mechanisms that govern the host range of viruses are incompletely understood. A small number of poxvirus genes have been identified that influence the host range of poxviruses. We show that the host range functions of E3 and K3, two host range factors from vaccinia virus, are a result of species-specific interactions with the antiviral protein kinase R (PKR) and that PKR from closely related species displayed dramatic differences in their sensitivities to these viral inhibitors. While there is a substantial body of work demonstrating host-specific interactions with K3, the current model for E3-mediated PKR inhibition is that E3 non-specifically sequesters dsRNA to prevent PKR activation. This model does not predict species-specific sensitivity to E3; therefore, our data suggest that the current model is incomplete, and that dsRNA sequestration is not the primary mechanism for E3 activity.
miRTarDS: High-Accuracy Refining Protein-level MicroRNA Target Interactions from Prediction Databases Using Sentence-BERT
Authors: Chen Baiming
Published: May 2024

MicroRNAs (miRNAs) regulate gene expression by binding to mRNAs, inhibiting translation, or promoting mRNA degradation. miRNAs are of great importance in the development of various diseases. Currently, numerous sequence-based miRNA target prediction tools are available, however, only 1% of their predictions have been experimentally validated. In this study, we propose a novel approach that leverages disease similarity degree between miRNAs and genes as a key feature to further refine human sequence-based predicted miRNA target interactions (MTIs). To quantify the similarity degree of diseases, we fine-tuned the Sentence-BERT model. Our method achieved an F1 score of 0.88 in accurately distinguishing human protein-level experimentally validated MTIs (functional MTIs, validated through western blot or reporter assay) and predicted MTIs. Moreover, this method exhibits exceptional generalizability across different databases. We applied the proposed method to analyze 1,220,904 human MTIs sourced from miRTarbase, miRDB, and miRWalk, encompassing 6,085 genes and 1,261 pre-miRNAs. Our model was trained in miRTarBase 2022. However, we accurately identified 90% (518/574) of the updated functional MTIs in miRTarbase 2025. This study has the potential to provide valuable insights into the understanding of miRNA-gene regulatory networks and to promote advancements in disease diagnosis, treatment, and drug development.
Detecting hidden order in fractional Chern insulators
Authors: Pauw F. , Palm F. A. , Schollwöck U. , Bohrdt A. , Paeckel S. , Grusdt F.
Published: May 2024

Topological phase transitions go beyond Ginzburg and Landau's paradigm of spontaneous symmetry breaking and occur without an associated local order parameter. Instead, such transitions can be characterized by the emergence of nonlocal order parameters, which require measurements on extensively many particles simultaneously—an impossible venture in real materials. On the other hand, quantum simulators have demonstrated such measurements, making them prime candidates for experimental confirmation of nonlocal topological order. Here, building upon the recent advances in preparing few-particle fractional Chern insulators using ultracold atoms and photons, we propose a realistic scheme for detecting the hidden off-diagonal long-range order (HODLRO) characterizing Laughlin states. Furthermore, we demonstrate the existence of this hidden order in fractional Chern insulators, specifically for the ν=1/2-Laughlin state in the isotropic Hofstadter-Bose-Hubbard model. This is achieved by large-scale numerical density matrix renormalization group (DMRG) simulations based on matrix product states, for which we formulate an efficient sampling procedure providing direct access to HODLRO in close analogy to the proposed experimental scheme. We confirm the characteristic power-law scaling of HODLRO, with an exponent 1/ν=2, and show that its detection requires only a few thousand snapshots. This makes our scheme realistically achievable with current technology and paves the way for further analysis of nonlocal topological orders, e.g., in topological states with non-Abelian anyonic excitations.

Published by the American Physical Society
2024
Superfluid-supersolid phase transition of elongated dipolar Bose-Einstein condensates at finite temperatures
Authors: Sánchez-Baena J. , Pohl T. , Maucher F.
Published: May 2024

We analyze the finite-temperature phase diagram of a dipolar Bose-Einstein condensate confined in a tubular geometry. The effect of thermal fluctuations is accounted for by means of Bogoliubov theory employing the local density approximation. In the considered geometry, the superfluid-supersolid phase transition can be of first and second order. We discuss how the corresponding transition point is affected by the finite temperature of the system.

Published by the American Physical Society
2024
Sustaining success: the power of relational bonding in building franchisee trust in South Korea’s food service industry
Authors: Koo Dong-Woo , Lee Sae-Mi
Published: May 2024

Purpose

Relationship marketing has emerged as pivotal, aiming to bolster collaboration and reduce uncertainty for both franchisors and franchisees. However, understanding the nuanced impact of relational bonding strategies – financial, social, and structural – on franchisee outcomes, particularly in South Korea’s food service industry, remains lacking. This study is an in-depth exploration of the nuanced impact of franchisors’ relational bonding strategies – structural, social, and economic – on critical franchisee outcomes in the food service industry.

Design/methodology/approach

By leveraging data from 496 franchisees in South Korea, our investigation meticulously delineates the unique contributions of these bonding strategies in enhancing franchisee’s social and economic satisfaction, building trust in franchisors and fostering long-term orientation among franchisees. This study unravels the complex mediating roles that satisfaction and trust play in the dynamic interplay between franchisors’ bonding efforts and the cultivation of enduring franchisee relationships.

Findings

The study reveals that structural, social, and economic bonding impact social satisfaction, while all relational bonding factors directly influence economic satisfaction. Structural and economic bonding influence trust in the franchisor, but social bonding does not. Economic and social satisfaction directly affect trust, and only economic satisfaction directly influences long-term orientation. Finally, trust in the franchisor positively affects long-term orientation.

Originality/value

We offer fresh insights into the strategic management of franchisor–franchisee relationships, aiming to enrich the literature on relationship marketing by highlighting the differential impacts and significance of distinct bonding strategies in promoting sustainable franchise partnerships.
Leadership training and development in the age of artificial intelligence
Authors: Sposato Martin
Published: May 2024

Purpose

The purpose of this study is to examine the multifaceted implications of AI on leadership dynamics and organizational practices. By synthesizing insights from behavioral theory, AI analytics, and ethical considerations, the study aims to equip leaders with the requisite knowledge, skills, and mindset to foster adaptive leadership, anticipate change, and cultivate innovation amidst AI-driven disruptions.

Design/methodology/approach

This article employs a qualitative research approach, integrating literature review and conceptual analysis to explore the intersection of leadership development and Artificial Intelligence (AI). Drawing insights from scholarly articles, theoretical frameworks and practice, the study elucidates the evolving landscape of leadership in the context of AI adoption. Practical action points are derived to guide organizational leaders and educators in navigating AI-induced transformations effectively.

Findings

The integration of AI into leadership dynamics necessitates a paradigm shift in leadership paradigms, emphasizing the fusion of technical proficiency with emotional intelligence. Behavioral theory coupled with AI analytics offers valuable insights into effective leadership behaviors, facilitating the design of tailored leadership development programs. Proactive leadership strategies, ethical considerations, and talent management emerge as pivotal factors in navigating AI-induced transformations and fostering organizational resilience.

Originality/value

This article contributes to the literature by synthesizing diverse perspectives on AI leadership and offering practical action points for organizational leaders and educators. By highlighting the integration of behavioral theory, AI analytics, and ethical considerations, the study underscores the importance of interdisciplinary approaches in leadership research and education. The insights derived from this study inform organizational practices, curriculum development in higher education, and future research agendas, fostering ethical AI adoption and cultivating adaptive leadership cultures in the age of Artificial Intelligence.
School-to-school partnerships: an approach to improving Syrian schools in post-conflict recovery
Authors: Alkalash Ibrahim , Alkalash Mohammad
Published: May 2024

Purpose

This research seeks to highlight school partnerships as an approach to improving schools and halting the deterioration of their performance in an environment that has suffered from the consequences of conflict for more than a decade.

Design/methodology/approach

The research used the qualitative method, and the data were collected through semi-structured interviews with 20 school leaders and teachers.

Findings

The results showed the presence of positive attitudes toward inter-school partnerships and their perception of many benefits, the most prominent of which was increasing social cohesion in school and surrounding communities that suffer from divisions resulting from conflict. A set of obstacles includes legislative obstacles, a low degree of autonomy, low competency of school leaders, a lack of trust and incentives.

Originality/value

This study proposes a range of solutions to address the challenges associated with building partnerships. The research emphasizes the significance the school-to-school partnerships and their positive role in improving the performance of schools in developing countries, especially in environments suffering from the consequences of civil wars and social divisions.
Model-free visual servoing based on active disturbance rejection control and adaptive estimator for robotic manipulation without calibration
Authors: Tian Jun , Zhong Xungao , Peng Xiafu , Hu Huosheng , Liu Qiang
Published: May 2024

Purpose

Visual feedback control is a promising solution for robots work in unstructured environments, and this is accomplished by estimation of the time derivative relationship between the image features and the robot moving. While some of the drawbacks associated with most visual servoing (VS) approaches include the vision–motor mapping computation and the robots’ dynamic performance, the problem of designing optimal and more effective VS systems still remains challenging. Thus, the purpose of this paper is to propose and evaluate the VS method for robots in an unstructured environment.

Design/methodology/approach

This paper presents a new model-free VS control of a robotic manipulator, for which an adaptive estimator aid by network learning is proposed using online estimation of the vision–motor mapping relationship in an environment without the knowledge of statistical noise. Based on the adaptive estimator, a model-free VS schema was constructed by introducing an active disturbance rejection control (ADRC). In our schema, the VS system was designed independently of the robot kinematic model.

Findings

The various simulations and experiments were conducted to verify the proposed approach by using an eye-in-hand robot manipulator without calibration and vision depth information, which can improve the autonomous maneuverability of the robot and also allow the robot to adapt its motion according to the image feature changes in real time. In the current method, the image feature trajectory was stable in the camera field range, and the robot’s end motion trajectory did not exhibit shock retreat. The results showed that the steady-state errors of image features was within 19.74 pixels, the robot positioning was stable within 1.53 mm and 0.0373 rad and the convergence rate of the control system was less than 7.21 s in real grasping tasks.

Originality/value

Compared with traditional Kalman filtering for image-based VS and position-based VS methods, this paper adopts the model-free VS method based on the adaptive mapping estimator combination with the ADRC controller, which is effective for improving the dynamic performance of robot systems. The proposed model-free VS schema is suitable for robots’ grasping manipulation in unstructured environments.
Sustainable investing in extreme market conditions: doing well while doing good
Authors: Valadkhani Abbas , O'Mahony Barry
Published: May 2024

Purpose

The aim of this study is to identify environmental, social and governance (ESG)-focused funds that can effectively uphold ethical principles while also delivering competitive financial returns by evaluating the performance of 24 well-established exchange-traded funds (ETFs). The study also compares the performance of four widely recognized ETFs representing NASDAQ (ticker: QQQ), S&P500 (SPY), Dow Jones (DIA) and Russell 2000 (IWM) with the sample of 24 ESG funds.

Design/methodology/approach

This paper utilizes four complementary measures, namely Sharpe, Sortino, Omega and Calmar ratios, to assess the risk-adjusted return performance of ETFs, with a particular emphasis on extreme downside risk.

Findings

The findings indicate that ESG-focused ETFs can predominantly outperform DIA and IWM in the last five years (1 November 2018–22 March 2023). However, when compared to QQQ and SPY, only ICLN, SUSA and DSI consistently delivered competitive risk-adjusted returns. The performance of DSI and SUSA is almost equivalent to QQQ and SPY even during the last ten years.

Practical implications

The paper conducts a risk-return analysis of alternative ESG investment funds, suggesting that not all ETFs are created equal and that careful selection is vital for achieving different investment objectives. It is imperative to recognize that past performance is not a reliable indicator of future outcomes, requiring consideration of other factors in the post-evaluation phase.

Social implications

The study provides evidence to support the “doing well while doing good” hypothesis, indicating that competitive returns are achievable while also engaging in socially responsible investment.

Originality/value

This study fills a vital gap in the literature on ESG investment by highlighting that the choice of funds stands as the primary factor responsible for the conflicting findings by previous studies.
Under the influence: the Kusile tender and state capture permeating the national prosecuting authority
Authors: Curlewis Llewelyn Gray , Carter Katelyn-Mae
Published: May 2024

Purpose

The purpose of this paper is to give light to the present order of state capture and corruption within South Africa at present. South Africans often consider the National Prosecuting Authority to be an independent body which is free of the corruption of the rest of the Government; however, the situation that surrounds the Kusile Tender will suggest otherwise.

Design/methodology/approach

This paper’s approach is purely qualitative using journal articles, textbooks, reports, periodicals, speeches and legislation as its basis. It is through a consolidation of this literature that this paper was formed.

Findings

This paper determines that even the National Prosecuting Authority of South Africa is not free from the scourge that is corruption through the depiction of the Kusile Tender. Within this tender, the National Prosecuting Authority entered into a non-prosecution agreement with a defendant, Asea Brown Boveri, which cannot be accounted for in the Criminal Procedure Act 51 of 1977.

Originality/value

The concept of state capture and corruption are not new to any jurisdiction, let alone South Africa. This paper, however, intends to give insight into how even the departments which the public believe to be (and are constitutionally mandated to be) independent can fall prey to corrupt dealings.