bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombospondin-1 promotes fibro-adipogenic stromal expansion and contractile dysfunction of the diaphragm in obesity
Authors: Buras Eric D. , Woo Moon-Sook , Verma Romil Kaul , Kondisetti Sri Harshita , Davis Carol S. , Claflin Dennis R. , Baran Kimber Converso , Michele Daniel E. , Brooks Susan V. , Chun Tae-Hwa
Published: August 2023

Pulmonary disorders impact 40-80% of individuals with obesity. Respiratory muscle dysfunction is linked to these conditions; however, its pathophysiology remains largely undefined. Mice subjected to diet-induced obesity (DIO) develop diaphragmatic weakness. Increased intra-diaphragmatic adiposity and extracellular matrix (ECM) content correlate with reductions in contractile force. Thrombospondin-1 (THBS1) is an obesity-associated matricellular protein linked with muscular damage in genetic myopathies. THBS1 induces proliferation of fibro-adipogenic progenitors (FAPs)—mesenchymal cells that differentiate into adipocytes and fibroblasts. We hypothesized that THBS1 drives FAP-mediated diaphragm remodeling and contractile dysfunction in DIO. We tested this by comparing effects of dietary challenge on diaphragms of wild-type (WT) andThbs1knockout (Thbs1-/-) mice. Bulk and single-cell transcriptomics demonstrated DIO-induced stromal expansion in WT diaphragms. Diaphragm FAPs displayed upregulation of ECM and TGFβ-related expression signatures, and augmentation of aThy1-expressing sub-population previously linked to type 2 diabetes. Despite similar weight gain,Thbs1-/-mice were protected from these transcriptomic changes, and from obesity-induced increases in diaphragm adiposity and ECM deposition. Unlike WT controls,Thbs1-/-diaphragms maintained normal contractile force and motion after DIO challenge. These findings establish THBS1 as a necessary mediator of diaphragm stromal remodeling and contractile dysfunction in overnutrition, and potential therapeutic target in obesity-associated respiratory dysfunction.
Co-Occurrence Network Analysis Reveals The Alterations Of The Skin Microbiome And Metabolome In Atopic Dermatitis Patients
Authors: Gomes Paulo Wender P. , Mannochio-Russo Helena , Mao Junhong , Zhao Haoqi Nina , Tipton Craig D. , Ancira Jacob , Dorrestein Pieter C. , Li Min
Published: August 2023

Skin microbiome can be altered in patients with Atopic Dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for better treatments and identify specific microbial or molecular biomarkers. This study investigates the skin microbiome and metabolome of healthy subjects and lesion (ADL) and non-lesion (ADNL) of AD patients by 16S rRNA gene sequencing and mass spectrometry, respectively. Samples from AD patients showed alterations in the diversity and composition of the skin microbiome.Staphylococcusspecies, especiallyS. aureus, were significantly increased in the ADL group. Metabolomic profiles were also different between the groups. Dipeptide-derived are more abundant in ADL, which may be related to skin inflammation. Co-occurrence network analysis was applied to integrate the microbiome and metabolomics data and revealed higher co-occurrence of metabolites and bacteria in healthy and ADNL compared to ADL.S. aureusco-occurred with dipeptide-derived in ADL, while phytosphingosine-derived compounds showed co-occurrences with commensal bacteria,e.g. Paracoccussp.,Pseudomonassp.,Prevotella bivia, Lactobacillus iners, Anaerococcussp.,Micrococcussp.,Corynebacterium ureicelerivorans, Corynebacterium massiliense, Streptococcus thermophilus, andRoseomonas mucosa, in healthy and ADNL groups. Therefore, these findings provide valuable insights into how AD affects the human skin metabolome and microbiome.

Importance

This study provides valuable insight into changes in the skin microbiome and associated metabolomic profiles. It also identifies new therapeutic targets that may be useful for developing personalized treatments for individuals with atopic dermatitis based on their unique skin microbiome and metabolic profiles.
Pneumatic Nano-Sieve for CRISPR-based Detection of Drug-resistant Bacteria
Authors: Peng Ruonan , Chen Xinye , Xu Fengjun , Hailstone Richard , Men Yujie , Du Ke
Published: August 2023

The increasing prevalence of antibiotic-resistant bacterial infections, particularly methicillin-resistant Staphylococcus aureus (MRSA), presents a significant public health concern. Timely detection of MRSA is crucial to enable prompt medical intervention, limit its spread, and reduce antimicrobial resistance. Here, we introduce a miniaturized nano-sieve device featuring a pneumatically-regulated chamber for highly efficient MRSA purification from human plasma samples. By using packed magnetic beads as a filter and leveraging the deformability of the nano-sieve channel, we achieve an on-chip concentration factor of 15 for MRSA. We integrated this device with recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas detection system, resulting in an on-chip limit of detection (LOD) of approximately 100 CFU/mL. This developed approach provides a rapid, precise, and centrifuge-free solution suitable for point-of-care diagnostics, with the potential to significantly improve patient outcomes in resource-limited medical conditions.
Perturbation of the insomniaWDR90GWAS locus pinpoints rs3752495 as a causal variant influencing distal expression of neighboring gene,PIG-Q
Authors: Sonti Shilpa , Littleton Sheridan H. , Pahl Matthew C. , Zimmerman Amber J. , Chesi Alessandra , Palermo Justin , Lasconi Chiara , Brown Elizabeth B. , Pippin James A. , Wells Andrew D. , Doldur-Balli Fusun , Pack Allan I. , Gehrman Phillip R. , Keene Alex C. , Grant S.F.A.
Published: August 2023

Although genome wide association studies (GWAS) have been crucial for the identification of loci associated with sleep traits and disorders, the method itself does not directly uncover the underlying causal variants and corresponding effector genes. The overwhelming majority of such variants reside in non-coding regions and are therefore presumed to impact the activity ofcis-regulatory elements, such as enhancers. Our previously reported ‘variant-to-gene mapping’ effort in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs), combined with validation in bothDrosophilaand zebrafish, implicatedPIG-Qas a functionally relevant gene at the insomnia ‘WDR90’ locus. However, importantly that effort did not characterize the corresponding underlying causal variant at this GWAS signal. Specifically, our genome-wide ATAC-seq and high-resolution promoter-focused Capture C datasets generated in this cell setting brought our attention to a shortlist of three tightly neighboring single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium in a candidate intronic enhancer region ofWDR90that contacted the openPIG-Qpromoter. The objective of this study was to investigate the influence of the proxy SNPs collectively and then individually onPIG-Qmodulation and to pinpoint the causal “regulatory” variant among the three SNPs. Starting at a gross level perturbation, deletion of the entire region harboring all three SNPs in human iPSC-derived neural progenitor cells via CRISPR-Cas9 editing and subsequent RNA sequencing revealed expression changes in specificPIG-Qtranscripts. Results from more refined individual luciferase reporter assays for each of the three SNPs in iPSCs revealed that the intronic region with the rs3752495 risk allele induced a ∼2.5-fold increase in luciferase expression (n=10). Importantly, rs3752495 also exhibited an allele specific effect, with the risk allele increasing the luciferase expression by ∼2-fold compared to the non-risk allele. In conclusion, our variant-to-function approach and subsequentin vitrovalidation implicates rs3752495 as a causal insomnia risk variant embedded at theWDR90-PIG-Qlocus.
Structural polymorphism of the nucleic acids in pentanucleotide repeats associated with CANVAS
Authors: Kudo Kenta , Hori Karin , Asamitsu Sefan , Maeda Kohei , Aida Yukari , Hokimoto Mei , Matsuo Kazuya , Yabuki Yasushi , Shioda Norifumi
Published: August 2023

Short tandem repeats are highly unstable, depending on repeat length, and the expansion of the repeat length in the human genome is responsible for repeat expansion disorders. Pentanucleotide AAGGG and ACAGG repeat expansions in intron 2 of the gene encoding replication factor C subunit 1 (RFC1) cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and other phenotypes of late-onset cerebellar ataxia. Herein, we reveal the structural polymorphism of theRFC1repeat sequences associated with CANVASin vitro. Single-stranded AAGGG repeat DNA formed a hybrid-type G-quadruplex, whereas its RNA formed a parallel-type G-quadruplex with three layers. The RNA of the ACAGG repeat sequence formed double helical hairpin structures comprising C-G and G-C base pairs with A:A and GA:AG mismatched repeats. Furthermore, both pathogenic repeat RNAs formed more rigid structures than those of the non-pathogenic sequences. These findings provide novel insights into the structural polymorphism of theRFC1repeat sequences, which may be closely related to the disease mechanism of CANVAS.
Purine biosynthesis pathways are required for myogenesis inXenopus laevis
Authors: Duperray Maëlle , Henriet Elodie , Saint-Marc Christelle , Boué-Grabot Eric , Daignan-Fornier Bertrand , Massé Karine , Pinson Benoît
Published: August 2023

Purines are required for fundamental biological processes and alterations in their metabolism lead to severe genetic diseases associated with developmental defects whose etiology remains unclear. Here, we studied the developmental requirements for purine metabolism using the amphibianXenopus laevisas a vertebrate model. We provide the first functional characterization of purine pathway-genes and show that these genes are mostly expressed in nervous and muscular embryonic tissues. Morphants were generated to decipher the functions of these genes, with a focus on the adenylosuccinate lyase (ADSL), an enzyme required for both salvage andde novopurine pathways.adsl.Lknock-down leads to severe reduction in the expression of the Myogenic Regulatory Factors (MRFs: Myod1, Myf5 and Myogenin), thus resulting in defects in somitogenesis and in the formation and/or migration of both craniofacial and hypaxial muscle progenitors. Similar alterations were observed upon reduced expression ofhprt1.Landppat, two genes specific to the salvage and thede novopathways, respectively. In conclusion, our data shows for the first time thatde novoand recycling purine pathways are essential for myogenesis and highlight new mechanisms in the regulation of MRFs gene expression.
Landscapes associated with Japanese encephalitis virus reflect the functional biogeography of waterbird species across Australia and the Central Indo-Pacific region
Authors: Walsh Michael G. , Webb Cameron , Brookes Victoria
Published: August 2023

Japanese encephalitis virus (JEV), a zoonotic, mosquito-borne virus, has broad circulation across the Central Indo-Pacific biogeographical region (CIPBR), which recently expanded dramatically within this region across southeastern Australia over the summer of 2021-2022. Preliminary investigation of the landscape epidemiology of the outbreaks of JEV in Australian piggeries found associations with particular landscape structure as well as ardeid species richness. The ways in which waterbird species from diverse taxonomic pools with substantial functional variation might couple with JEV-associated landscape structure was not explored, and therefore, key questions regarding the landscape epidemiology and infection ecology of JEV remain unanswered. Moreover, given the established presence of JEV within the CIBPR, the extent to which waterbird species pools in JEV-associated landscapes in Australia reflect broader regional patterns in functional biogeography presents a further knowledge gap particularly with respect to potential virus dispersal via maintenance hosts. The current study investigated waterbird species presence, ecological traits, and functional diversity distribution at landscape scale, and how these aligned with confirmed JEV detections in eastern Australia and the wider CIPBR. The results showed that waterbird habitat associated with JEV detection in Australia in 2022 and more widely across the CIPBR over the last 20 years reflects a range of species representing 8 families in 4 orders (ardeids, anatids, rallids, phalacrocoracids, threskiornithids, gruids, and pelecanids). Increasing waterbird functional diversity (trait-based mean pairwise dissimilarity) was associated with landscapes delineating JEV occurrence, while only one individual trait, high hand-wing index, was consistently associated with species presence in these JEV-associated landscapes in both Australia and the broader CIPBR. This suggests that dispersal capacity among the waterbird species pools that dominate JEV-associated landscapes might be important. By taking an agnostic approach to JEV maintenance host status, this study indicates a relatively large, CIPBR-wide pool of waterbird families associated with JEV landscapes, challenging the narrow view that JEV maintenance is limited to ardeid birds. In addition, these findings highlight the potential for leveraging functional biogeography in high-risk landscapes across broad geographic extent to guide landscape-specific selection of species for JEV surveillance.
Cooperation between bacteriocytes and endosymbionts drives function and development of symbiotic cells in mussel holobionts
Authors: Chen Hao , Li Mengna , Zhong Zhaoshan , Wang Minxiao , Lian Chao , Han Guanghui , Wang Hao , Zhou Li , Zhang Huan , Cao Lei , Li Chaolun
Published: August 2023

Symbiosis drives the adaptation and evolution in multicellular organisms. Modeling the function and development of symbiotic cells/organs in holobionts is yet challenging. Here, we surveyed the molecular function and developmental trajectory of bacteriocyte lineage in non-model deep-sea mussels by constructing a high-resolution single-cell expression atlas of gill tissue. We show that mussel bacteriocytes optimized immune processes to facilitate recognition, engulfment, and elimination of endosymbionts, and interacted with them intimately in sterol, carbohydrate, and ammonia metabolism. Additionally, the bacteriocytes could arise from three different stem cells as well as bacteriocytes themselves. In particular, we showed that the molecular functions and developmental process of bacteriocytes were guided by the same set of regulatory networks and dynamically altered regarding to symbiont abundance via sterol-related signaling. The coordination in the functions and development of bacteriocytes and between the host and symbionts underlies the interdependency of symbiosis, and drives the deep-sea adaptation of mussels.
Mentoring practices predictive of doctoral student outcomes in a biological sciences cohort
Authors: Debray Reena , Dewald-Wang Emily A. , Ennis Katherine K.
Published: August 2023

Despite the importance of a diversity of backgrounds and perspectives in biological research, women, racial and ethnic minorities, and students from non-traditional academic backgrounds remain underrepresented in the composition of university faculty. Through a study on doctoral students at a research-intensive university, we pinpoint advising from faculty as a critical component of graduate student experiences and productivity. Graduate students from minority backgrounds reported lower levels of support from their advisors and research groups. However, working with an advisor from a similar demographic background substantially improved productivity and well-being of these students. Several other aspects of mentoring practices positively predicted student success and belonging, including frequent one-on-one meetings, empathetic and constructive feedback, and relationships with other peer or faculty mentors. Our study highlights the need to renovate graduate education with a focus on retention – not just recruitment – to best prepare students for success in scientific careers.
13C-SpaceM: Spatial single-cell isotope tracing reveals heterogeneity ofde novofatty acid synthesis in cancer
Authors: Buglakova Elena , Ekelöf Måns , Schwaiger-Haber Michaela , Schlicker Lisa , Molenaar Martijn R. , Mohammed Shahraz , Stuart Lachlan , Eisenbarth Andreas , Hilsenstein Volker , Patti Gary J. , Schulze Almut , Snaebjornsson Marteinn T. , Alexandrov Theodore
Published: August 2023

Metabolism has emerged as a key factor in homeostasis and disease including cancer. Yet, little is known about the heterogeneity of metabolic activity of cancer cells due to the lack of tools to directly probe it. Here, we present a novel method,13C-SpaceM for spatial single-cell isotope tracing of glucose-dependentde novolipogenesis. The method combines imaging mass spectrometry for spatially-resolved detection of13C6-glucose-derived13C label incorporated into esterified fatty acids with microscopy and computational methods for data integration and analysis. We validated13C-SpaceM on a spatially-heterogeneous normoxia-hypoxia model of liver cancer cells. Investigating cultured cells, we revealed single-cell heterogeneity of lipogenic acetyl-CoA pool labelling degree upon ACLY knockdown that is hidden in the bulk analysis and its effect on synthesis of individual fatty acids. Next, we adapted13C-SpaceM to analyze tissue sections of mice harboring isocitrate dehydrogenase (IDH)-mutant gliomas. We found a strong induction ofde novofatty acid synthesis in the tumor tissue compared to the surrounding brain. Comparison of fatty acid isotopologue patterns revealed elevated uptake of mono-unsaturated and essential fatty acids in the tumor. Furthermore, our analysis uncovered substantial spatial heterogeneity in the labelling of the lipogenic acetyl-CoA pool indicative of metabolic reprogramming during microenvironmental adaptation. Overall,13C-SpaceM enables novel ways for spatial probing of metabolic activity at the single cell level. Additionally, this methodology provides unprecedented insight into fatty acid uptake, synthesis and modification in normal and cancerous tissues.
eQTL mapping in transgenic alpha-synuclein carryingCaenorhabditis elegansrecombinant inbred line
Authors: Huang Yuqing , Wang Yiru A. , van Sluijs Lisa , Vogels Demi H. J. , Chen Yuzhi , Tegelbeckers Vivian I. P. , Schoonderwoerd Steven , Riksen Joost A.G. , Kammenga Jan E. , Harvey Simon C. , Sterken Mark G.
Published: August 2023

Protein aggregation of α-synuclein (αS) is a genetic and neuropathological hallmark of Parkinson’s disease (PD). Studies in the model nematodeCaenorhabditis eleganssuggested that variation of αS aggregation depends on the genetic background. However, which genes and genetic modifiers underlie individual differences in αS pathology remains unknown. To study the genotypic-phenotypic relationship of αS aggregation, we constructed a Recombinant Inbred Line (RIL) panel derived from a cross between genetically divergent strainsC. elegansNL5901 and SCH4856, both harboring the human αS gene. As a first step to discover genetic modifiers 70 αS-RILs were measured for whole-genome gene expression and expression quantitative locus analysis (eQTL) were mapped. We detected multiple eQTL hot-spots, many of which were located on Chromosome V. To confirm a causal locus, we developed Introgression Lines (ILs) that contain SCH4856 introgressions on Chromosome V in an NL5901 background. We detected 74 genes with an interactive effect between αS and the genetic background, including the human p38 MAPK homologuepmk-1that has previously been associated with PD. Together, we present a unique αS-RIL panel for defining effects of natural genetic variation on αS pathology, which contributes to finding genetic modifiers of PD.
Tip60-mediated Rheb acetylation links palmitic acid with mTORC1 activation and insulin resistance
Authors: Zhao Zengqi , Chen Qiang , Xiang Xiaojun , Dai Weiwei , Fang Wei , Cui Kun , Li Baolin , Liu Qiangde , Liu Yongtao , Shen Yanan , Li Yueru , Xu Wei , Mai Kangsen , Ai Qinghui
Published: August 2023

Differences in dietary fatty acid saturation impact glucose homeostasis and insulin sensitivity in vertebrates. Excess dietary intake of saturated fatty acids (SFAs) induces glucose intolerance and metabolic disorders. In contrast, unsaturated fatty acids (UFAs) elicit beneficial effects on insulin sensitivity. However, it remains elusive how SFAs and UFAs signal differentially toward insulin signaling to influence glucose homeostasis. Here, using a croaker model, we report that dietary palmitic acid (PA), but not oleic acid or linoleic acid, leads to dysregulation of mTORC1 signaling which provokes systemic insulin resistance and glucose intolerance. Mechanistically, using croaker primary myocytes, mouse C2C12 myotubes and HEK293T cells, we show that PA-induced mTORC1 activation is dependent on mitochondrial fatty acid β oxidation. Notably, PA profoundly elevates acetyl-CoA derived from mitochondrial fatty acid β oxidation which intensifies Tip60-mediated Rheb acetylation. Subsequently, the induction of Rheb acetylation facilitates hyperactivation of mTORC1 which enhances serine phosphorylation of IRS1 and simultaneously inhibits transcription of IRS1 through impeding TFEB nuclear translocation, leading to impairment of insulin signaling. Furthermore, targeted abrogation of acetyl-CoA produced from fatty acid β oxidation or Tip60-mediated Rheb acetylation by pharmacological inhibition and genetic knockdown rescues PA-induced insulin resistance. Collectively, this study reveals a conserved acetylation-dependent mechanistic insight for understanding the link between fatty acids and insulin resistance, which may provide a potential therapeutic avenue to intervene in the development of T2D.
Using a Deep Generation Network Reveals Neuroanatomical Specificity in Hemispheres
Authors: Wang Gongshu , Jiang Ning , Ma Yunxiao , Yan Tianyi
Published: August 2023

Asymmetry is an important property of brain organization, but its nature is still poorly understood. Capturing the neuroanatomical components specific to each hemisphere facilitates the understanding of the establishment of brain asymmetry. Since deep generative networks (DGNs) have powerful inference and recovery capabilities, we use one hemisphere to predict the opposite hemisphere by training the DGNs, which automatically fit the built-in dependencies between the left and right hemispheres. After training, the reconstructed images approximate the homologous components in the hemisphere. We use the difference between the actual and reconstructed hemispheres to measure hemisphere-specific components due to asymmetric expression of environmental and genetic factors. The results show that our model is biologically plausible and that our proposed metric of hemispheric specialization is reliable, representing a wide range of individual variation. Together, this work provides promising tools for exploring brain asymmetry and new insights into self-supervised DGNs for representing the brain.
Nanopores reveal the stoichiometry of single oligo-adenylates produced by type III CRISPR-Cas
Authors: Fuentenebro-Navas David , Steens Jurre A. , de Lannoy Carlos , Noordijk Ben , de Ridder Dick , Staals Raymond H.J. , Schmid Sonja
Published: August 2023

Cyclic oligoadenylates (cOAs) are small second messenger molecules produced by the type III CRISPR-Cas system as part of the prokaryotic immune response. The role of cOAs is to allosterically activate downstream effector proteins that induce dormancy or cell death, and thus abort viral spread through the population. Interestingly, different type III systems have been reported to utilize different cOA stoichiometries (with 3 to 6 adenylate monophosphates). However, so far, their characterization has only been possible in bulk and with sophisticated equipment, while a portable assay with single-molecule resolution has been lacking. Here, we demonstrate the label-free detection of single cOA molecules using a simple protein nanopore assay. It sensitively identifies the stoichiometry of individual cOA molecules and their mixtures from synthetic and enzymatic origin. To achieve this, we trained a convolutional neural network (CNN) and validated it with a series of experiments on mono- and polydisperse cOA samples. Ultimately, we determined the stoichiometric composition of cOAs produced enzymatically by the CRISPR type III-A and III-B variants ofThermus thermophilus. Interestingly, both variants produce cOAs of nearly identical composition, and we discuss the biological implications of this finding. The presented nanopore-CNN workflow with single-cOA resolution can be adapted to many other signaling molecules (including eukaryotic ones), and it may be integrated into portable handheld devices with potential point-of-care applications.
Integrative assessment of total and intact HIV-1 reservoir by a five-region multiplexed Rainbow digital PCR assay
Authors: Delporte Mareva , van Snippenberg Willem , Blomme Evy E. , Rutsaert Sofie , Verschoore Maxime , De Smet Evelien , De Scheerder Marie-Angélique , Gerlo Sarah , Vandekerckhove Linos , Trypsteen Wim
Published: August 2023

Persistent latent reservoirs of intact HIV-1 proviruses, capable of rebounding despite suppressive ART, hinder efforts towards an HIV-1 cure. Hence, assays specifically quantifying intact proviruses are crucial to assess the impact of curative interventions. Clinical trials have utilized two recent assays: intact proviral DNA assay (IPDA) and Q4PCR. While IPDA is more sensitive due to amplifying short fragments, it may overestimate intact fractions by relying only on two small regions. Q4PCR is sequencing-based and its performance might be subjected to bias against full-length proviruses. Leveraging digital PCR (dPCR) advancements, we developed the ‘Rainbow’ 5-plex proviral HIV-1 DNA assay, assessing it with standard materials and samples from 69 PLWH. The Rainbow assay proved equally sensitive but more specific than IPDA, is not subjected to bias against full-length proviruses, enabling high-throughput quantification of total and intact reservoir size. This innovation offers potential for targeted evaluation and monitoring of rebound-competent reservoirs, contributing to HIV-1 management and cure strategies.

Teaser

The 5 color ‘HIV-1 Rainbow’ digital PCR assay offers a multi-level view on the HIV reservoir in one snapshot reaction.
Russula(Basidiomycota, Russulales, Russulaceae) subsect.Roseinae“down under”
Authors: Buyck Bart , Horak Egon , Cooper Jerry A. , Song Yu
Published: August 2023

The present contribution presents species ofRussulasubsect.RoseinaeSarnari from the southern hemisphere.Russula incrustataBuyck, sp. nov. andR. koniamboensisBuyck, sp. nov. are described from New Caledonia,R. purpureotinctaR. F. R. McNabb from New Zealand is redescribed in detail and two secotioid species,R. albobrunneaT. Lebel from Australia andR. kermesina(R. F. R. McNabb) T. Lebel from New Zealand are shown to be the first known secotioid taxa inRoseinae. The systematic placement and importance of these southern taxa is discussed.
Infralimbic parvalbumin neural activity facilitates cued threat avoidance
Authors: Ho Yi-Yun , Yang Qiuwei , Boddu Priyanka , Bulkin David A. , Warden Melissa R.
Published: August 2023

The infralimbic cortex (IL) is essential for flexible behavioral responses to threatening environmental events. Reactive behaviors such as freezing or flight are adaptive in some contexts, but in others a strategic avoidance behavior may be more advantageous. IL has been implicated in avoidance, but the contribution of distinct IL neural subtypes with differing molecular identities and wiring patterns is poorly understood. Here, we study IL parvalbumin (PV) interneurons in mice as they engage in active avoidance behavior, a behavior in which mice must suppress freezing in order to move to safety. We find that activity in inhibitory PV neurons increases during movement to avoid the shock in this behavioral paradigm, and that PV activity during movement emerges after mice have experienced a single shock, prior to learning avoidance. PV neural activity does not change during movement toward cued rewards or during general locomotion in the open field, behavioral paradigms where freezing does not need to be suppressed to enable movement. Optogenetic suppression of PV neurons increases the duration of freezing and delays the onset of avoidance behavior, but does not affect movement toward rewards or general locomotion. These data provide evidence that IL PV neurons support strategic avoidance behavior by suppressing freezing.
BioE3 enables the identification ofbona fidetargets of E3 ligases
Authors: Barroso-Gomila Orhi , Merino-Cacho Laura , Muratore Veronica , Perez Coralia , Taibi Vincenzo , Maspero Elena , Azkargorta Mikel , Iloro Ibon , Trulsson Fredrik , Vertegaal Alfred C. O. , Mayor Ugo , Elortza Felix , Polo Simona , Barrio Rosa , Sutherland James D.
Published: August 2023

The post-translational modification of proteins by ubiquitination is a highly regulated process that involves a dynamic, three-step enzymatic cascade, where more than 600 E3 ligases play a critical role in recognizing specific substrates for modification. Separatingbona fidetargets of E3s from E3-interacting proteins remains a major challenge in the field. In this study, we present BioE3, a novel approach for identifying substrates of ubiquitin-like (UbL) E3 ligases of interest. Using BirA-E3 ligase fusion proteins and bioUbLs, the method facilitates site-specific biotinylation of UbL-modified substrates of particular E3s for proteomic identification. We demonstrate that the BioE3 system can identify both known and novel targets of two RING-type ubiquitin E3 ligases: RNF4, known to be involved in DNA damage response and the regulation of PML nuclear bodies, and MIB1, implicated in endocytosis, autophagy, and centrosomal protein homeostasis. We further show the versatility of BioE3 by identifying targets of an organelle-specific E3 (MARCH5) and a relatively uncharacterized E3 (RNF214). Furthermore, we show that BioE3 works with HECT-type E3 ligases and identify novel targets of NEDD4 involved in vesicular trafficking. BioE3 is a powerful tool that enables identification ofbona fidesubstrates of UbL E3 ligases and how they change with chemical perturbations. BioE3 may also be applicable for UbLs beyond Ub and SUMO, as well as other E3 ligase classes. The resulting knowledge can shed light on the regulation of cellular processes by the complex UbL network and provide information useful for strategies such as targeted protein degradation (TPD), advancing our understanding of fundamental biological mechanisms and their applications.
Transcription termination factor ρ polymerizes under stress
Authors: Wang Bing , Said Nelly , Hilal Tarek , Finazzo Mark , Wahl Markus C. , Artsimovitch Irina
Published: August 2023

Bacterial RNA helicase ρ is a genome sentinel that terminates synthesis of damaged and junk RNAs that are not translated by the ribosome. Co-transcriptional RNA surveillance by ρ is essential for quality control of the transcriptome during optimal growth. However, it is unclear how bacteria protect their RNAs from overzealous ρ during dormancy or stress, conditions common in natural habitats. Here we used cryogenic electron microscopy, biochemical, and genetic approaches to show that residue substitutions, ADP, or ppGpp promote hyper-oligomerization ofEscherichia coliρ. Our results demonstrate that nucleotides bound at subunit interfaces control ρ switching from active hexamers to inactive higher-order oligomers and extended filaments. Polymers formed upon exposure to antibiotics or ppGpp disassemble when stress is relieved, thereby directly linking termination activity to cellular physiology. Inactivation of ρ through hyper-oligomerization is a regulatory strategy shared by RNA polymerases, ribosomes, and metabolic enzymes across all life.
The apoptotic, inflammatory, and fibrinolytic actions of vasoinhibin are in a motif different from its antiangiogenic HGR motif
Authors: Robles Juan Pablo , Zamora Magdalena , Garcia-Rodrigo Jose F. , Perez Alma Lorena , Bertsch Thomas , Martinez de la Escalera Gonzalo , Triebel Jakob , Clapp Carmen
Published: August 2023

Vasoinhibin is a proteolytic fragment of the hormone prolactin that inhibits blood vessel growth (angiogenesis) and permeability, stimulates the apoptosis and inflammation of endothelial cells and promotes fibrinolysis. The antiangiogenic and antivasopermeability properties of vasoinhibin were recently traced to the HGR motif located in residues 46 to 48, allowing the development of potent, orally active, HGR-containing vasoinhibin analogs for therapeutic use against angiogenesis-dependent diseases. However, whether the HGR motif is also responsible for the apoptotic, inflammatory, and fibrinolytic properties of vasoinhibin has not been addressed. Here, we report that HGR-containing analogs are devoid of these properties. Instead, the incubation of human umbilical vein endothelial cells with oligopeptides containing the sequence HNLSSEM, corresponding to residues 30 to 36 of vasoinhibin, induced apoptosis, the nuclear translocation of NF-κB, the expression of genes encoding leukocyte adhesion molecules (VCAM1andICAM1) and proinflammatory cytokines (IL1B, IL6, TNF), and the adhesion of peripheral blood leukocytes. Also, the intravenous or intra-articular injection of HNLSSEM-containing oligopeptides induced the expression ofVcam1, Icam1, Il1b, Il6, Tnfin the lung, liver, kidney, eye, and joints of mice and, like vasoinhibin, these oligopeptides promoted the lysis of plasma fibrin clots by binding to plasminogen activator inhibitor-1 (PAI-1). Moreover, the inhibition of PAI-1, urokinase plasminogen activator receptor, or NF-κB prevented the apoptotic and inflammatory actions. In conclusion, the functional properties of vasoinhibin are segregated into two different structural determinants. Because apoptotic, inflammatory, and fibrinolytic actions may be undesirable for antiangiogenic therapy, HGR-containing vasoinhibin analogs stand as selective and safe agents for targeting pathological angiogenesis.
Revisiting the structures and phase transitions of Ba2NaNb5O15
Authors: Grendal Ola G. , Evans Donald M. , Aamlid Solveig S.
Published: August 2023

The room-temperature and low-temperature structure(s) of Ba2NaNb5O15 (BNN) have been debated since the structure was proposed in the 1960s. This work revisits the structures and phase transitions of BNN, combining high-resolution X-ray and neutron powder diffraction with density functional theory calculations. Temperature-dependent high-resolution X-ray powder diffraction patterns are collected from 4 to 918 K, and sequential batch Rietveld refinement using a symmetry mode approach to describe the structure is used to extract the main structural changes as a function of temperature. The data show that the average structure of BNN is best described by the Ama2 space group, and no other structural phase transitions were observed below the ferroelastic transition. The symmetry mode analysis, combining results from diffraction and density functional theory, shows significant octahedral tilting and corrugations of both the A1 and A2 sites along the c direction. A strong correlation between the spontaneous strain and the octahedral tilting was observed, and a potential connection with emerging microstructure at low temperatures is proposed, all enabled by the symmetry mode approach used in this work.
Effects of information on salary satisfaction during the COVID-19 pandemic: an equity-based mediation model
Authors: Montalvo-Arroyo Sandra , de la Torre-Ruiz José Manuel , Vidal-Salazar María Dolores , Cordón-Pozo Eulogio
Published: August 2023

Purpose

This research aims to study the effects of information (on salary, salary reductions and the pandemic's impact on the organization) on the salary satisfaction of workers whose salary had been cut during the coronavirus disease 2019 (COVID-19) pandemic, analyzing the mediating role of salary equity in this relationship.

Design/methodology/approach

Information was acquired with a structured questionnaire sent by email in May 2021 from 251 employees in Spain during the “third wave” of COVID-19. The model was estimated using the weighted least squares mean and variance adjusted (WLSMV).

Findings

Results collected reveal that workers' perceptions of equity fully mediated the relationship between salary information, information on salary cuts and salary satisfaction.

Practical implications

Learning more about the effects of information on salary satisfaction can contribute to communication policies that reduce the negative impact of sensitive salary decisions, practical implications for employees, organizations and policymakers.

Originality/value

This study examines the central role of organizational information as a mechanism for managing problems arising from the pandemic-induced unfavorable working conditions. This study analyzes how this information affects workers' attitudes, highlighting the role of equity as a mediator in this process.
Resilience in the face of crisis: investigating COVID-19 impacts on urban community gardens in Greater Toronto Area, Canada
Authors: Robillard Paige , Sekercioglu Fatih , Edge Sara , Young Ian
Published: August 2023

Purpose

Urban community gardens (UCGs) are important sources of community, food and greenspaces in urban environments. Though UCGs in the Greater Toronto Area (GTA) of Ontario, Canada, were considered essential during the COVID-19 lockdowns and therefore open to gardeners, the impact of the COVID-19 pandemic on food security and UCG use among garden members and managers is not fully understood.

Design/methodology/approach

This was an exploratory qualitative study. Semi-structured interviews were conducted with seven managers and eight members of nine gardens in the GTA. The data were analyzed using thematic analysis.

Findings

The results suggest that UCGs helped participants be resilient to COVID-19 pandemic-related stressors through the provision of cultural ecosystem services. Therefore, this study supports the current literature that UCGs can help foster resilience during crises. While participants in this study did not end up being food insecure, participants did express concern about community food security.

Practical implications

Results contribute to the current body of literature, and can be used to further update and develop UCG policies, as well as help develop UCG infrastructure and management strategies for future crises.

Originality/value

The impacts of the pandemic on Canadian UCGs are not well understood. This research paper investigated the impact of the pandemic on UCG use and food security, as well as the link between UCG use and increased resilience to COVID-19-related stressors.
Effect of cognitive bias on the consumption of broiler products in China; the role of information acquisition channels
Authors: Lin Huiqi , Li Xi , Xu Siyu , He Jun , Aziz Noshaba
Published: August 2023

Purpose

Broiler meat is the most commonly used meat product worldwide. Although China is regarded as one of the three largest broiler producers, the per capita chicken consumption remains low. Consumers' cognitive bias and the information acquisition channels are believed to be the main factors contributing to this. This paper aims to discuss the aforementioned issue.

Design/methodology/approach

To explore the phenomenon empirically, the current study uses the survey data of 1,056 consumers from China and analyses them using ordered logistic regression.

Findings

The results revealed that consumers' cognitive bias significantly affects their behaviour toward broiler products, and the order of influence is cognitive bias regarding industry cognitive > product nutrition and taste > food safety. The study further revealed that the more diverse the information acquisition channels, the more likely they are to promote consumer behaviour toward broiler chickens. The order of influence of the channels was self-organising > new media > traditional media.

Practical implications

Overall, the findings suggest that the government and enterprises should strengthen and upgrade information channels to boost both the broiler industry and consumer consumption behaviour regarding poultry products.

Originality/value

Rather than the usual focus on the impact of consumer cognition on consumer behaviour, this study examines the impact of cognitive bias on consumer behaviour. Further, centring on broiler products with high protein, low fat and feed-to-meat ratios, this study explores the reasons the per capita consumption of broiler products in China is far lower than the national average.
Enhancing quality requirements management in retailing industry: The role of Quality Function Deployment
Authors: Pacheco Diego A. de J. , Caetano Rodrigo Veleda , Bonato Samuel Vinícius , dos Santos Bruno Miranda , Bueno Wagner Pietrobelli
Published: August 2023

Purpose

Small retail stores in the luxury market face significant challenges due to fluctuations in market demand. This task turns challenging as it requires effectively coordinating and translating customer needs into specific requirements that align with retail goals and available resources. However, limited empirical research exists investigating how managers can address service value and quality attributes in small retail stores. This article aims to bridge this gap by investigating the role of quality function deployment (QFD) in improving market and quality requirements management in small retail stores.

Design/methodology/approach

Based on the case study, a customer survey was initially conducted to gather information on critical characteristics valued in the luxury retail segment. QFD was used to assist the company in identifying and prioritizing key quality attributes to meet customer requirements effectively.

Findings

The findings demonstrate that implementing QFD in small luxury retail stores empowers managers to identify previously neglected product and service quality aspects. The article shows that QFD informs organizational adaptations that align with the demands of the retail market, leading to an improved ability to meet customer expectations and enhance customer value through the development of enhanced products and services. The study showcases the efficacy of the tested methodology in effectively capturing and prioritizing both tangible and intangible customer needs in retail.

Practical implications

Findings offer valuable insights to retail managers of small luxury stores, providing actionable market-oriented strategies. By implementing the recommended practices, managers can improve the store’s competitiveness and better cater to the customer base.

Originality/value

This study contributes to bridging persistent knowledge gaps by addressing the unique context of small luxury retail stores and introducing the application of QFD in this setting. The insights gained from this research are relevant to both retailing and quality management literature. Considering the growing prevalence of transformations in the retail industry, the study provides practical implications for retail managers in effectively navigating these changes.
The key role played by innovation in the talent management and organizational performance relationship
Authors: Luna-Arocas Roberto
Published: August 2023

Purpose

The key aspect of this study is the mediating role of innovation in the relationship between talent management (TM) and organizational performance (OP).

Design/methodology/approach

A structural equation model with AMOS software is used to gauge the impact of TM on innovation and OP. In this regard, innovation is the mediating variable of the model. The author uses Hayes PROCESS macro for SPSS (Hayes, 2018) and the mediating procedure of Baron and Kenny's model (1986).

Findings

Results show that innovation is a full mediating variable that captures the whole variance of the model in the relationship between TM and OP.

Practical implications

The results of this study are important for organizations since they emphasize the need to adapt TM strategies to innovation and improvement in the organization. This involves not only managers and their training and development plans but also employees in their attraction, development and retention strategies.

Originality/value

The originality of this study is that it explores the causal relationship between the three variables considered in the model, that is, TM, innovation and OP. These relationships evidence gaps in human resource management and TM literature, improving current understanding of the role of innovation in the organizational context.
Examination of research efficiency of research universities in Türkiye by data envelopment analysis
Authors: Maral Muammer
Published: August 2023

Purpose

The purpose of this study is to examine the research efficiency of the research universities in Türkiye and to identify potential areas for improvement and to examine the factors affecting efficiency.

Design/methodology/approach

For this purpose, data envelopment analysis was conducted with the output-oriented Banker, Charnes and Cooper (BCC) model with five-year article and citation counts data of 23 universities which were obtained from the Web of Science Core Collection.

Findings

The findings of the study show that only eight research universities are efficient. There are areas of development for universities to be effective. In addition, the findings of the regression analysis conducted to reveal the determinants of efficiency revealed significant results.

Research limitations/implications

Research universities in Türkiye should allocate their resources in a way to increase research performance. Policies should be developed to increase the number of publications and, more importantly, the quality of publications.

Originality/value

Potential areas for improvement were identified for the universities to become efficient. The results revealed that both publication quality and productivity need to be improved, but there is more room for improvement in publication quality. Regression analysis with the determinants of efficiency scores shows that the development level of the region where the universities are located has a positive effect on the research efficiency of universities. In addition, it is concluded that smaller universities have better efficiency scores.
Lessons from the road less travelled: student teachers' and newly qualified teachers' experiences of mentoring in the Irish further education and training sector
Authors: Mellon Conor
Published: August 2023

Purpose

Mentoring processes and relationships can prove crucial to teachers in the initial phases of the teacher education continuum. Limited research exists regarding mentoring in further education and training (FET) in Ireland. This paper attempts to address this gap, illuminating and unpacking the “mentoring stories” of five teachers in FET.

Design/methodology/approach

The overall project adopted a narrative approach. Data were collected via in-depth interviews, part of which clearly focussed on participants' lived experience of mentoring. Thematic analysis revealed four overarching themes.

Findings

The themes reveal a spectrum of practices and perspectives on the role of mentors. There are ample instances of collegiality, mutual respect and an appreciation of the professional life stage of the mentee. However, evidently a lack of understanding of who mentors are and what they do persists, leading to some informal approaches and opening up the potential for misinterpretation and misalignment.

Originality/value

This paper sheds light on an area of FET practice that has been relatively unseen before now. It gives voice to those who have experienced mentoring in the Irish FET sector that, to a degree, has seen structural and attitudinal transformations in recent times.