bluuebunny/crossref_metadata_2025_split huggingface dataset:
PI(3,4,5)P3 allosteric regulation of repressor activator protein 1 controls antigenic variation in trypanosomes
Authors: Touray Abdoulie O. , Rajesh Rishi , Isebe Tony , Sternlieb Tamara , Loock Mira , Kutova Oksana , Cestari Igor 
Published: May 2023

AbstractAfrican trypanosomes evade host immune clearance by antigenic variation, causing persistent infections in humans and animals. These parasites express a homogeneous surface coat of variant surface glycoproteins (VSGs). They transcribe one out of hundreds of VSG genes at a time from telomeric expression sites (ESs) and periodically change the VSG expressed by transcriptional switching or recombination. The mechanisms underlying the control of VSG switching and its developmental silencing remain elusive. We report that telomeric ES activation and silencing entail an on/off genetic switch controlled by a nuclear phosphoinositide signaling system. This system includes a nuclear phosphatidylinositol 5-phosphatase (PIP5Pase), its substrate PI(3,4,5)P3, and the repressor-activator protein 1 (RAP1). RAP1 binds to ES sequences flanking VSG genes via its DNA binding domains and represses VSG transcription. In contrast, PI(3,4,5)P3 binds to the N-terminus of RAP1 and controls its DNA binding activity. Transient inactivation of PIP5Pase results in the accumulation of nuclear PI(3,4,5)P3, which binds RAP1 and displaces it from ESs, activating transcription of silent ESs and VSG switching. The system is also required for the developmental silencing of VSG genes. The data provides a mechanism controlling reversible telomere silencing essential for the periodic switching in VSG expression and its developmental regulation.
RAD51-mediated R-loop formation acts to repair transcription-associated DNA breaks driving antigenic variation inTrypanosoma brucei
Authors: Girasol Mark John , Krasilnikova Marija , Marques Catarina A. , Damasceno Jeziel D. , Lapsley Craig , Lemgruber Leandro , Burchmore Richard , Beraldi Dario , Carruthers Ross , Briggs Emma M. , McCulloch Richard 
Published: May 2023

AbstractRNA-DNA hybrids are epigenetic features of all genomes that intersect with many processes, including transcription, telomere homeostasis and centromere function. Increasing evidence suggests RNA-DNA hybrids can provide two conflicting roles in the maintenance and transmission of genomes: they can be the triggers of DNA damage, leading to genome change, or can aid the DNA repair processes needed to respond to DNA lesions. Evasion of host immunity by African trypanosomes, such asTrypanosoma brucei, relies on targeted recombination of silent Variant Surface Glycoprotein (VSG) genes into a specialised telomeric locus that directs transcription of just oneVSGfrom thousands. How suchVSGrecombination is targeted and initiated is unclear. Here, we show that a key enzyme ofT. bruceihomologous recombination, RAD51, interacts with RNA-DNA hybrids. In addition, we show that RNA-DNA hybrids display a genome- wide co-localisation with DNA breaks, and that this relationship is impaired by mutation of RAD51. Finally, we show that RAD51 acts to repair highly abundant, localised DNA breaks at the single transcribedVSG, and that mutation of RAD51 alters RNA-DNA hybrid abundance both around the transcribedVSGand across the silentVSGarchive. This work reveals a widespread, generalised role for RNA-DNA hybrids in directing RAD51 activity during recombination and uncovers a specialised application of this interplay during targeted DNA break repair needed for the criticalT. bruceiimmune evasion reaction of antigenic variation.
Spatial heterogeneity in carbohydrates and their utilisation by microbes in the high North Atlantic
Authors: Priest Taylor , Vidal-Melgosa Silvia , Hehemann Jan-Hendrik , Amann Rudolf , Fuchs Bernhard M. 
Published: May 2023

ABSTRACTCarbohydrates are chemically and structurally diverse, represent a substantial fraction of marine organic matter and are key substrates for heterotrophic microbes. Studies on carbohydrate utilisation by marine microbes have been centred on phytoplankton blooms in temperate regions, while far less is known from high-latitude waters and during later seasonal stages. Here, we combine glycan microarrays and analytical chromatography with metagenomics and metatranscriptomics to show the spatial heterogeneity in glycan distribution and their utilisation by microbes in Atlantic waters of the Arctic during late summer. The composition and abundance of monomers and glycan structures in POM varied with location and depth. Complex fucose-containing sulfated polysaccharides, known to accumulate in the ocean, were consistently detected, suggesting limited degradation by microbes. In contrast, the more labile β-1,3-glucan exhibited a patchy distribution, indicating local variations in primary productivity and rapid utilisation. Metatranscriptomics showed active and dynamic microbial populations that targeted specific glycans. Gene transcription of carbohydrate-active enzymes revealed narrow substrate niches for specialists, involving compounds such as α-mannans and alginate, along with the targeting of communal substrates, such as laminarin, by multiple populations. The observed spatial heterogeneity indicates that local biological and physical processes continue to shape the carbohydrate pool during late summer in high latitude waters and microbial populations are active and responsive to such changes.
Mapping cells through time and space with moscot
Authors: Klein Dominik , Palla Giovanni , Lange Marius , Klein Michal , Piran Zoe , Gander Manuel , Meng-Papaxanthos Laetitia , Sterr Michael , Bastidas-Ponce Aimée , Tarquis-Medina Marta , Lickert Heiko , Bakhti Mostafa , Nitzan Mor , Cuturi Marco , Theis Fabian J. 
Published: May 2023

AbstractSingle-cell genomics technologies enable multimodal profiling of millions of cells across temporal and spatial dimensions. Experimental limitations prevent the measurement of all-encompassing cellular states in their native temporal dynamics or spatial tissue niche. Optimal transport theory has emerged as a powerful tool to overcome such constraints, enabling the recovery of the original cellular context. However, most algorithmic implementations currently available have not kept up the pace with increasing dataset complexity, so that current methods are unable to incorporate multimodal information or scale to single-cell atlases. Here, we introduce multi-omics single-cell optimal transport (moscot), a general and scalable framework for optimal transport applications in single-cell genomics, supporting multimodality across all applications. We demonstrate moscot’s ability to efficiently reconstruct developmental trajectories of 1.7 million cells of mouse embryos across 20 time points and identify driver genes for first heart field formation. The moscot formulation can be used to transport cells across spatial dimensions as well: To demonstrate this, we enrich spatial transcriptomics datasets by mapping multimodal information from single-cell profiles in a mouse liver sample, and align multiple coronal sections of the mouse brain. We then present moscot.spatiotemporal, a new approach that leverages gene expression across spatial and temporal dimensions to uncover the spatiotemporal dynamics of mouse embryogenesis. Finally, we disentangle lineage relationships in a novel murine, time-resolved pancreas development dataset using paired measurements of gene expression and chromatin accessibility, finding evidence for a shared ancestry between delta and epsilon cells. Moscot is available as an easy-to-use, open-source python package with extensive documentation athttps://moscot-tools.org.
A Single Site Mutation Tunes Fluorescence and Chromophorylation of an Orange Fluorescent Cyanobacteriochrome
Authors: Janis Makena K. , Zou Wenping , Zastrow Melissa L. 
Published: May 2023

AbstractCyanobacteriochrome (CBCR) GAF domains bind bilin cofactors to confer sensory wavelengths important for various cyanobacterial photosensory processes. Many isolated GAF domains autocatalytically bind bilins, becoming fluorescent. The third GAF domain of CBCR Slr1393 fromSynechocystissp. PCC6803 binds phycocyanobilin (PCB) natively, yielding red/green photoswitching properties but also binds phycoerythrobilin (PEB). GAF3-PCB has low quantum yields but non-photoswitching GAF3-PEB is brighter, making it a promising platform for new genetically encoded fluorescent tools. GAF3, however, shows low PEB binding efficiency (chromophorylation) at ∼3% compared to total protein expressed inE. coli. Here we explored site-directed mutagenesis and plasmid-based methods to improve GAF3-PEB binding and demonstrate its utility as a fluorescent marker in live cells. We found that a single mutation improved chromophorylation while tuning the emission over ∼30 nm, likely by shifting autoisomerization of PEB to phycourobilin (PUB). Plasmid modifications also improved chromophorylation and moving from a dual to single plasmid system facilitated exploration of a range of mutants via site saturation mutagenesis and sequence truncation. Collectively, the PEB/PUB chromophorylation was raised by ∼7-fold. Moreover, we show that protein-chromophore interactions can tune autoisomerization of PEB to PUB in a GAF domain, which will facilitate future engineering of similar GAF domain-derived fluorescent proteins.
Age-dependent Powassan Virus Lethality and Neuropathogenesis in Mice
Authors: Mladinich Megan C. , Himmler Grace E. , Conde Jonas N. , Gorbunova Elena E. , Schutt William R. , Tsirka Stella , Kim Hwan Keun , Mackow Erich R. 
Published: May 2023

ABSTRACTPowassan viruses (POWV) are emergent tick-borne flaviviruses that cause severe neurologic disease in humans. Subcutaneous inoculation of C57BL/6 mice with POWV (strain LI9) resulted in overt brain damage resembling spongiform encephalitis. Noting higher POWV lethality in older mice, we assessed neurovirulence as a function of age. We found that POWV LI9 inoculation was lethal in 80% of 50 wk old mice, 10-15 dpi, and that lethality was sequentially reduced in 40, 30, 20, 10 wk old mice to <10%. Lethality was conferred by 2-20 POWV FFUs, and POWV neuropathology was evident as early as 5 dpi, with lethal disease 10-15 dpi correlated with sustained POWV RNA levels in brains of aged mice. Histology of POWV infected 50 wk old murine brains revealed severe spongiform neuronal necrosis, microgliosis, and inflammation with increased brainstem and cerebellar damage. These findings delineate an age-dependent murine model of lethal POWV infection that mirrors human POWV disease and permits analysis of age-dependent neurovirulence determinants.SignificanceOur findings establish a novel age-dependent lethal animal model to study encephalitic POWV diseasein vivo. These initial findings demonstrate that following peripheral inoculation, non-neuroadapted POWV LI9 is neuroinvasive and enters the brains of young and aged mice. However, POWV LI9 lethality is strictly age-dependent and correlated with increased viral load in the brains of aged mice. POWV rapidly directs neuronal loss and spongiform lesions, microglial activation and causes prolonged inflammation that fails to clear POWV from the brains of aged mice. Our results provide a lethal murine model of POWV neurovirulence that mirrors the prevalence of severe human POWV encephalitis in the elderly. This lethal murine POWV model provides mechanisms for defining POWV protective responses of the young, revealing determinants of age-dependent POWV lethality and evaluating potential POWV therapeutics.SUMMARYPowassan virus is an emerging tick-borne flavivirus linked to severe neurologic disease in aged individuals. Here we describe an age-dependent mouse model of POWV pathogenesis.SUBJECTSPowassan virus, flavivirus, neurovirulence, neuroinvasion, neurotropic, spongiform encephalopathy, microgliosis, neuroinflammation
Transcript errors generate a continuous stream of amyloid and prion-like proteins in human cells
Authors: Chung Claire S. , Kou Yi , Shemtov Sarah J. , Verheijen Bert M. , Flores Ilse , Love Kayla , Dosso Ashley Del , Thorwald Max , Liu Yuchen , Toney Renaldo G. , Carrillo Lucy , Nguyen Megan , Biao Huang , Jin Yuxin , Jauregui Ashley Michelle , Quiroz Juan Diaz , Moore Darcie L. , Simpson Stephen , Thomas Kelley , Coba Marcelo P. , Li Zhongwei , Benayoun Bérénice A. , Rosenthal Joshua , Kennedy Scott , Quadrato Giorgia , Gout Jean-Francois , Chen Lin , Vermulst Marc 
Published: May 2023

ABSTRACTAging is characterized by the accumulation of amyloid and prion-like proteins. However, the molecular mechanisms by which these proteins arise remain unclear. Here, we demonstrate that transcript errors generate amyloid and prion-like proteins in a wide variety of human cell types, including stem cells, brain organoids, and fully differentiated neurons. Intriguingly, some of these proteins are identical to proteins previously implicated in familial cases of amyloid diseases, raising the possibility that both familial and non-familial cases are caused by identical mutant proteins. However, transcript errors also generate amyloid proteins that have not been observed before, suggesting that aging cells are exposed to a second class of pathogenic proteins we are currently unaware of. Finally, we show that transcript errors are readily generated by DNA damage, a hallmark of human aging and a staple of multiple proteotoxic diseases, including Alzheimer’s disease. Together, these observations greatly expand our understanding of mutagenesis in human aging and disease and suggest a new mechanism by which amyloid diseases can develop.
Within-host rhinovirus evolution in upper and lower respiratory tract highlights capsid variability and mutation-independent compartmentalization
Authors: Makhsous Negar , Goya Stephanie , Avendaño Carlos , Rupp Jason , Kuypers Jane , Jerome Keith R. , Boeckh Michael , Waghmare Alpana , Greninger Alexander L 
Published: May 2023

AbstractBackgroundHuman rhinovirus (HRV) infections can progress from the upper (URT) to lower (LRT) respiratory tract in immunocompromised individuals, causing high rates of fatal pneumonia. Little is known about how HRV evolves within hosts during infection.MethodsWe sequenced HRV complete genomes from 12 hematopoietic cell transplant patients with prolonged infection for up to 190 days from both URT (nasal wash, NW) and LRT (bronchoalveolar lavage, BAL) specimens. Metagenomic (mNGS) and amplicon-based NGS were used to study the emergence and evolution of intra-host single nucleotide variants (iSNVs).ResultsIdentical HRV intra-host populations in matched NW and BAL specimens indicated no genetic adaptation is required for HRV to progress from URT to LRT. Microbial composition between matched NW and BAL confirmed no cross-contamination during sampling procedure. Coding iSNVs were 2.3-fold more prevalent in capsid over non-structural genes, adjusted for length. iSNVs modeled onto HRV capsid structures were significantly more likely to be found in surface residues, but were not preferentially located in known HRV neutralizing antibody epitopes. Newly emergent, serotype-matched iSNV haplotypes from immunocompromised individuals from 2008-2010 could be detected in Seattle-area community HRV sequences from 2020-2021.ConclusionHRV infections in immunocompromised hosts can progress from URT to LRT with no specific evolutionary requirement. Capsid proteins carry the highest variability and emergent mutations can be detected in other, including future, HRV sequences.
Endoplasmic-Reticulum stress controls PIN-LIKES abundance and thereby growth adaptation
Authors: Waidmann Sascha , Beziat Chloe , Ferreira Da Silva Santos Jonathan , Feraru Elena , Feraru Mugurel I. , Sun Lin , Noura Seinab , Boutté Yohann , Kleine-Vehn Jürgen 
Published: May 2023

AbstractExtreme environmental conditions eventually limit plant growth (1, 2). Here we reveal an unprecedented mechanism that enables multiple external cues to get integrated into auxin-dependent growth programs inArabidopsis thaliana. Our forward genetics approach on dark grown hypocotyls uncovered that an imbalance in membrane lipids enhances the protein abundance of PIN-LIKES (PILS) (3–5) auxin transport facilitators at the endoplasmic reticulum (ER), which thereby limits nuclear auxin signaling and growth rates. We show that this subcellular response relates to ER stress signaling, which directly impacts on PILS protein turnover in a tissue-dependent manner. This mechanism allows PILS proteins to integrate environmental input with phytohormone auxin signaling, contributing to stress-induced growth adaptation in plants.
Organizational capabilities and SSCM: a bibliographic review and cluster analysis
Authors: Orioli Felipe Porphirio , Veríssimo José Manuel Cristóvão 
Published: May 2023

Purpose The purpose of the study is to perform a scientific mapping and detect the evolution pattern of two emerging fields, organizational capabilities and sustainable supply chain management (SSCM), to detect and visualize the existing conceptual domains and identify less-explored areas.Design/methodology/approach This study uses a methodological combination involving systematic literature review and bibliometric analysis. The methodology was implemented in the following order: definition and selection of the material using an electronic database, descriptive analysis of the material, category selection using bibliographic coupling analysis by VOSviewer (clusterization), material evaluation and content analysis.Findings The research results clarify the intellectual structure within the academic field. The authors’ identified three main clusters: (1) sustainable capabilities and practices in supply chain management (SCM), (2) green SCM and performance and (3) information technology and innovation. The findings reveal that there is a rich field to be explored, especially regarding issues involving sustainable technological capabilities, sustainable initiatives and key resource development.Practical implications This study facilitates researchers’ and practitioners’ understanding and their ability to map the different paths and evolution of SSCM and organizational capabilities. It can encourage managers and policymakers alike to conceive new approaches to engage in the adoption of SSCM.Originality/value This work employs a singular approach to identify the intellectual knowledge and topics related to the implementation of SSCM by adopting the theoretical approach of sustainable organizational capacity. It contributes to the debate on distinguishing specific sustainable organizational capabilities from traditional capabilities.
Readjusting the speed of leverage adjustment during the COVID-19 pandemic?
Authors: Tarkom Augustine , Huang Xinhui 
Published: May 2023

PurposeRecognizing the severity of COVID-19 on the US economy, the authors investigate the behavior of US-listed firms towards leverage speed of adjustment (SOA) during the pandemic. While prior evidence (based on an international study) shows that firm leverage increased during the pandemic leading to a higher SOA toward leverage ratios, leverage for US firms during the same period reduced drastically. Yet there is a dearth of empirical studies on the behavior of US-listed firms' SOA during the pandemic. The authors fill this void.Design/methodology/approachThe study includes US-listed non-financial and non-utility firms for the period 2015Q1-2021Q4, covering a total sample of 45,213 firm-quarter observations. The authors’ empirical strategy is based on the generalized method of moments (GMM) and firm-fixed effect methodology, controlling for firm- and quarter-fixed effects.FindingsThree main findings are established: (1) while the SOA toward book target increased during the pandemic, SOA toward market target increased significantly only for less valued and cash-constrained firms; (2) firms in states most impacted by the pandemic adjusted faster towards target ratio; and (3) while the emergence of the pandemic and the overall firm-level risk increased (decreased) the deviation from book (market) target, firm-level risk partially mediated the effect of the pandemic on how far firms deviated from target ratio.Practical implicationsThis study enhances our understanding of leverage adjustment during the crisis and shows that risk avoidance motive and the market value of firms are key determinants of convergence rate during the crisis and further demonstrates that market leverage is more sensitive to market dynamics. As such, caution must be taken when dealing with and interpreting market leverage SOA.Originality/valueAlthough prior evidence based on international study provides insights into how firms behave toward their leverage ratios because of the pandemic, little is known about how US firms react to the pandemic in terms of the target ratios, particularly (1) since the USA is one of the severely affected countries and (2) firms in the USA reduced their leverage ratios as against what prior evidence shows. The authors provide evidence to explain how and why US firms reacted toward their SOA during the pandemic.
Rejoinder: fractures in the edifice of PLS
Authors: Rönkkö Mikko , Lee Nick , Evermann Joerg , McIntosh Cameron , Antonakis John 
Published: May 2023

Purpose
This study aims to provide a response to the commentary by Yuan on the paper “Marketing or Methodology” in this issue of EJM.

Design/methodology/approach
Conceptual argument and statistical discussion.

Findings
The authors find that some of Yuan’s arguments are incorrect, or unclear. Further, rather than contradicting the authors’ conclusions, the material provided by Yuan in his commentary actually provides additional reasons to avoid partial least squares (PLS) in marketing research. As such, Yuan’s commentary is best understood as additional evidence speaking against the use of PLS in real-world research.

Research limitations/implications
This rejoinder, coupled with Yuan’s comment, continues to support the strong implication that researchers should avoid using PLS in marketing and related research.

Practical implications
Marketing researchers should avoid using PLS in their work.

Originality/value
This rejoinder supports the earlier conclusions of “Marketing or Methodology,” with additional argumentation and evidence.
Income shock and financial well-being in the COVID-19 pandemic: financial resilience and psychological resilience as mediators
Authors: Kulshreshtha Amrita , Raju Sk , Muktineni Sai Manasa , Chatterjee Devlina 
Published: May 2023

PurposeThe purpose of this study was to investigate the relationship between income shock suffered during the coronavirus pandemic and subsequent financial well-being (FWB) of Indian adults, mediated by financial resilience (FR) and psychological resilience (PR).Design/methodology/approachThe authors propose a conceptual model for the relationship between income shock and FWB, with FR and PR as mediator variables. The authors consider four dimensions of financial resilience: economic resources, financial inclusion, financial knowledge and social capital. This study uses a unidimensional scale for PR. Data were collected from 370 respondents from 11 cities across India. Structural equation models were built to test the proposed hypotheses.FindingsIncome shock was negatively associated with FWB. Estimated path coefficients for FR and PR were statistically significant and confirmed a mediating role. Among the four dimensions of financial resilience, only economic resources were positively associated with FWB. The mediation relation between economic resources and FWB was larger than PR.Research limitations/implicationsSince convenience sampling was used to collect data, the results of this study are indicative but not generalizable.Social implicationsFor individuals who suffered income shocks during the pandemic, adequate economic resources are crucial for FWB. Governmental disbursements, personal savings and medical or life insurance could provide an adequate safety net.Originality/valueThere are no extant studies that examine the association between income shocks and FWB in the pandemic, and this study contributes to the literature.