bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional redundancy revealed by the deletion of the mimivirus GMC-oxidoreductase genes
Authors: Alempic Jean-Marie , Bisio Hugo , Villalta Alejandro , Santini Sébastien , Lartigue Audrey , Schmitt Alain , Bugnot Claire , Notaro Anna , Belmudes Lucid , Adrait Annie , Poirot Olivier , Ptchelkine Denis , De Castro Cristina , Couté Yohann , Abergel Chantal 
Published: April 2023

AbstractThe mimivirus 1.2Mb genome was shown to be organized into a nucleocapsid-like genomic fiber encased in the nucleoid compartment inside the icosahedral capsid (1). The genomic fiber protein shell is composed of a mixture of two GMC-oxidoreductase paralogs, one of them being the main component of the glycosylated layer of fibrils at the surface of the virion (2). In this study, we determined the effect of the deletion of each of the corresponding genes on the genomic fiber and the layer of surface fibrils. First, we deleted the GMC-oxidoreductase the most abundant in the genomic fiber, and determined its structure and composition in the mutant. As expected, it was composed of the second GMC-oxidoreductase and contained 5- and 6-start helices similar to the wild-type fiber. This result led us to propose a model explaining their coexistence. Then, we deleted the GMC-oxidoreductase the most abundant in the layer of fibrils to analyze its protein composition in the mutant. Second, we showed that the fitness of single mutants and the double mutant were not decreased compared to the wild-type viruses in laboratory conditions. Third, we determined that deleting the GMC-oxidoreductase genes did not impact the glycosylation or the glycan composition of the layer of surface fibrils, despite modifying their protein composition. Since the glycosylation machinery and glycan composition of members of different clades are different (3, 4), we expanded the analysis of the protein composition of the layer of fibrils to members of the B and C clades and showed that it was different among the three clades and even among isolates within the same clade. Taken together, the results obtained on two distinct central processes (genome packaging and virion coating) illustrate an unexpected functional redundancy in members of the familyMimiviridae, suggesting this may be the major evolutionary force behind their giant genomes.One-Sentence SummaryFunctional redundancy preserves mimivirus genomic fiber and layer of fibrils formation.
Genetic context controls early microglia-synaptic interactions in mouse models of Alzheimer’s disease
Authors: Heuer Sarah E. , Keezer Kelly J. , Hewes Amanda A. , Onos Kristen D. , Graham Kourtney C. , Howell Gareth R. , Bloss Erik B. 
Published: April 2023

ABSTRACTCommon features of Alzheimer’s disease (AD) include amyloid pathology, microglia activation and synaptic dysfunction, however, the causal relationships amongst them remains unclear. Further, human data suggest susceptibility and resilience to AD neuropathology is controlled by genetic context, a factor underexplored in mouse models. To this end, we leveraged viral strategies to label an AD-vulnerable neuronal circuit in CA1 dendrites projecting to the frontal cortex in genetically diverse C57BL/6J (B6) and PWK/PhJ (PWK)APP/PS1mouse strains and used PLX5622 to non-invasively deplete brain microglia. Reconstructions of labeled neurons revealed microglia-dependent changes in dendritic spine density and morphology in B6 wild-type (WT) andAPP/PS1yet a marked stability of spines across PWK mice. We further showed that synaptic changes depend on direct microglia-dendrite interactions in B6.APP/PS1but not PWK.APP/PS1mice. Collectively, these results demonstrate that microglia-dependent synaptic alterations in a specific AD-vulnerable projection pathway are differentially controlled by genetic context.
The trade-off between individual metabolic specialization and versatility determines the metabolic efficiency of microbial communities
Authors: Wang Miaoxiao , Chen Xiaoli , Fang Yuan , Zheng Xin , Huang Ting , Nie Yong , Wu Xiao-Lei 
Published: April 2023

AbstractIn microbial systems, a metabolic pathway can be either completed by one autonomous population or alternatively be distributed among a consortium performing metabolic division of labor (MDOL), where several specialized populations cooperate to complete the pathway. MDOL facilitates the system’s function by reducing the metabolic burden; however, it may also hinder the function by reducing the exchange efficiency of metabolic intermediates among individuals. As a result, the metabolic efficiency of a community is influenced by trade-offs between the metabolic specialization and versatility of individuals, with the latter potentially introducing metabolic redundancy into the community. However, it remains unclear how metabolic specialization and versatility of the individuals involved can be controlled in order to optimize the function of the community. In this study, we deconstructed the metabolic pathway of naphthalene degradation into four specialized steps and introduced them individually or combinatorically into different strains, with varying levels of metabolic specialization. Using these strains, we engineered 1,456 synthetic consortia with varying levels of metabolic redundancy and tested their naphthalene degradation efficiency. We found that 74 consortia possessing metabolic redundancy exhibited higher degradation efficiency than both the autonomous population and the rigorous MDOL community. Quantitative modeling derived from our experiments provides general strategies for identifying the most effective MDOL consortium with functional redundancy (MCFR) from a range of possible MCFRs. Our large-scale genomic analysis suggests that natural communities for hydrocarbon degradation are mostly functionally redundant. In summary, our study provides critical insights into the engineering of high-performance microbial systems and explains why functional redundancy is prevalent in natural microbial communities.
Longitudinal brain structure changes in Parkinson’s disease: a replication study
Authors: Sokołowski Andrzej , Bhagwat Nikhil , Chatelain Yohan , Dugré Mathieu , Hanganu Alexandru , Monchi Oury , McPherson Brent , Wang Michelle , Poline Jean-Baptiste , Sharp Madeleine , Glatard Tristan 
Published: April 2023

AbstractContextAn existing major challenge in Parkinson’s disease (PD) research is the identification of biomarkers of disease progression. While Magnetic Resonance Imaging (MRI) is a potential source of PD biomarkers, none of the MRI measures of PD are robust enough to warrant their adoption in clinical research. This study is part of a project that aims to replicate 11 PD studies reviewed in a recent survey (JAMA neurology, 78(10) 2021) to investigate the robustness of PD neuroimaging findings to data and analytical variations.ObjectiveThis study attempts to replicate the results in Hanganu et al. (Brain, 137(4) 2014) using data from the Parkinson’s Progression Markers Initiative (PPMI).MethodsUsing 25 PD subjects and 18 healthy controls, we analyzed the rate of change of cortical thickness and of the volume of subcortical structures, and we measured the relationship between MRI structural changes and cognitive decline. We compared our findings to the results in the original study.ResultsSimilarly to the original study, PD patients with mild cognitive impairment (MCI) exhibited increased cortical thinning over time compared to patients without MCI in the right middle temporal gyrus, insula, and precuneus. (2) The rate of cortical thinning in the left inferior temporal and precentral gyri in PD patients correlated with the change in cognitive performance. (3) There were no group differences in the change of subcortical volumes. (4) We did not find a relationship between the change in subcortical volumes and the change in cognitive performance.ConclusionDespite important differences in the dataset used in this replication study, and despite differences in sample size, we were able to partially replicate the original results. We produced a publicly available reproducible notebook allowing researchers to further investigate the reproducibility of the results in Hanganu et al. (2014) when more data becomes available in PPMI.
Translation in a Box: Orthogonal Evolution in theSaccharomyces cerevisiaeMitochondrion
Authors: Rothschild-Mancinelli Brooke , Alvarez-Carreño Claudia , Guo Wenying , Ito Chieri , Costa Alex , Petrov Anton S. , Lobachev Kirill , Williams Loren Dean 
Published: April 2023

AbstractThe ability to re-engineer and creatively evolve the translation system (TS) would allow invention of new coded polymers by altering the amino acid sidechain inventory and by shifting the polypeptide backbone into new chemical spaces. Unfortunately, the TS is difficult to manipulate and is more constrained over evolution than any other biological system. An orthogonal TS, running in parallel to the primary TS within a given host cell, would release constraints and allow TS manipulation. A fully orthogonal TS requires dedicated rRNAs, rProteins, aminoacyl-tRNA synthetases, and initiation and termination factors, none of which interact with the primary TS. TheS. cerevisiaemitochondrial TS is fully orthogonal to the cytosolic TS. Mito-rRNAs, mito- rProteins, mito-tRNAs, mito-aminoacyl tRNA synthetases, and mito-translation factors are distinct from, physically separated from, and functionally independent of their cytosolic counterparts. Here, theS. cerevisiaemitochondrial translation system was subjected to various stresses including antibiotics, mutagenesis and truncation of mito-rProteins, or wholesale replacement of mito-rProteins. Directed evolution of these stressed systems was facilitated by controlled transitions between fermentation and respiration, by changing the carbon source in the growth medium; the dependence ofS. cerevisiaesurvival on mitochondrial translation can be toggled on and off. Specific recreation of the resulting mutations recapitulate the evolved phenotypes. The method developed here appears to be a general approach for discovering functional dependencies. Suppressor mutations reveal functional dependencies within theS. cerevisiaemitochondrial TS. For example proteins Rrg9 or Mrx1 interact with the mito-TS and have critical role in its function. The combined results indicate that theS. cerevisiaemitochondrial TS can be engineered and evolved in isolation of the cytosolic TS.SignificanceThe Central Dogma of Molecular Biology rules life on Earth. Information flows from DNA to mRNA to protein. In the last step of the Central Dogma, the translation system decodes mRNA and produces coded proteins by linking amino acids into polymers. Engineering and evolving the translation system could permits full technical control over this process and could lead to the generation of novel polymers. Here, we use the mitochondrial translation system in the budding yeastSaccharomyces cerevisiaefor directed evolution of translation. We modify and evolve the translation system both directly and indirectly using antibiotics and gene editing tools and then measure resulting functionality. Our results show this secondary translation system insideS. cerevisiaemitochondria can be used as an approach for translation engineering.
Hippocampal neural fluctuation between memory encoding and retrieval states during a working memory task in humans
Authors: Watanabe Yusuke , Ikegaya Yuji , Yanagisawa Takufumi 
Published: April 2023

AbstractBackgroundWorking memory (WM) is essential for everyday life, yet its neural mechanism remains unclear. Although the hippocampus plays a critical role in memory consolidation and retrieval, its role in WM tasks has yet to be fully elucidated. We hypothesized that multiunit activities in the hippocampus alter their representations depending on the memory load and phase of a WM task, particularly in relation to sharp-wave ripple complexes (SWRs), which are known as various cognitive biomarkers.MethodsWe used an open dataset of intracranial electroencephalogram (iEEG) data and multiunit activity recorded from the medial temporal lobe (MTL) of nine patients with epilepsy. The MTL includes the hippocampus, entorhinal cortex, and amygdala. During the recording, all subjects performed an eight-second Sternberg test, in which they memorized sets of four, six, or eight letters (encoding phase), waited for three seconds (maintenance phase), and recalled whether a probe letter was included (Match IN task) or not (Mismatch OUT task) (retrieval phase). We used Gaussian-process factor analysis to visualize the neural trajectories of multiunit activity in MTL regions during the task. We also detected SWRs from the iEEG data in the hippocampus.FindingsWe found that the trajectory distance between phases of the Sternberg task was larger in the hippocampus compared to the entorhinal cortex and amygdala. Additionally, the trajectory distance between the encoding and retrieval phases was memory load dependent. Moreover, a transient trajectory increase was detected during SWRs. Finally, the trajectory direction of the hippocampus fluctuated between the encoding and retrieval states, and the balance of the fluctuation was shifted to the retrieval state during SWR periods.InterpretationOur results demonstrate the involvement of the hippocampus during a WM task. Furthermore, it is suggested that SWR in the retrieval phase plays a role in memory retrieval for a WM task. Our results provide new insight into the two-stage model of memory formation.
Plasticity of host cell organelles in response to Pb infection
Authors: Djavaheri Mohammad , Clothier Leah , Kindrachuk Colin , Borhan M. Hossein 
Published: April 2023

AbstractPlasmodiophora brassicae(Pb) is the most important member of the plant pathogenic protist subgroup, Rhizaria.Pbis an obligate soil-borne plant root pathogen which makes the study ofPbbiology and its interaction with its host challenging. To overcome this challenge, we adopted an axenic cell culture method to study the interaction ofPbwith its host plantBrassica spp. at the cellular and molecular levels.Pb, during its life cycle within the host, was confined to the cytoplasm of the infected cells. Our results showed that upon Pb infection, the dynamics of the plant cell organelles including mitochondria, plastids, nuclei, vacuoles, vesicles were altered. Both Plant’s and parasite’sdiacylglycerol acyltransferases(DGAT) genes were highly expressed in the calli, which indicated a need for the oil accumulation at the switch between replication and growth stages of the pathogen. This notion was supported by the accumulation of oil bodies that were only observed inside the pathogen cells. Our results also indicated that starch was utilized by thePbin infected cells, an indication thatPbinduces cell viability by altering the host carbon metabolism. The ongoing dynamic changes in the infected plant cell organelles suggest that plant responds toPbinfection, through the induction of organellar plasticity.
Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis
Authors: Unterman Avraham , Zhao Amy Y. , Neumark Nir , Schupp Jonas C. , Ahangari Farida , Cosme Carlos , Sharma Prapti , Flint Jasper , Stein Yan , Ryu Changwan , Ishikawa Genta , Sumida Tomokazu S. , Gomez Jose L. , Herazo-Maya Jose , Cruz Charles S. Dela , Herzog Erica L. , Kaminski Naftali 
Published: April 2023

AbstractRationaleChanges in peripheral blood cell populations have been observed but not detailed at single-cell resolution in idiopathic pulmonary fibrosis (IPF).ObjectivesTo provide an atlas of the changes in the peripheral immune system in stable and progressive IPF.MethodsPeripheral blood mononuclear cells (PBMCs) from IPF patients and controls were profiled using 10x Chromium 5’ single-cell RNA sequencing (scRNA-seq). Flow cytometry was used for validation. Protein concentrations of Regulatory T-cells (Tregs) and Monocytes chemoattractants were measured in plasma and lung homogenates from patients and controls.Measurements and Main ResultsThirty-eight PBMC samples from 25 patients with IPF and 13 matched controls yielded 149,564 cells that segregated into 23 subpopulations, corresponding to all expected peripheral blood cell populations. Classical monocytes were increased in progressive and stable IPF compared to controls (32.1%, 25.2%, 17.9%, respectively, p<0.05). Total lymphocytes were decreased in IPF vs controls, and in progressive vs stable IPF (52.6% vs 62.6%, p=0.035). Tregs were increased in progressive IPF (1.8% vs 1.1%, p=0.007), and were associated with decreased survival (P=0.009 in Kaplan-Meier analysis). Flow cytometry analysis confirmed this finding in an independent cohort of IPF patients. Tregs were also increased in two cohorts of lung scRNA-seq. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF.ConclusionsThe single-cell atlas of the peripheral immune system in IPF, reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs).
Migrant healthcare workers’ experiences and mobility patterns in a global health crisis: a qualitative study with Romania physicians working in Germany
Authors: Kuhlmann Ellen , Ungureanu Marius-Ionuț , Thilo Nancy , Fehr Leonie Mac , Cosma Nicoleta-Carmen , Brînzac Monica Georgina , Dopfer-Jablonka Alexandra 
Published: April 2023

AbstractIntroductionAttention to the healthcare workforce has increased, yet comprehensive information on migrant healthcare workers is missing. This study focuses on migrant healthcare workers’ experiences and explores mobility patterns in the middle of a global health crisis, aiming to explore the capacity for circular migration and support effective equitable healthcare workforce policy.MethodsRomanian physicians in Germany served as an empirical case study. We applied a qualitative explorative approach; interviews (n=21) were collected from mid of September to early November 2022 and content analysis was performed.ResultsMigrant physicians showed strong resilience during the COVID-19 crisis and rarely complained. Commitment to high professional standards and career development were major pull factors towards Germany, while perceptions of limited career choices, nepotism and corruption in Romania caused strong push mechanisms. We identified two major mobility patterns that may support circular migration policies: well-integrated physicians with a wish to give something back to their home country, and mobile cosmopolitan physicians who flexibly balance career opportunities and personal/family interests.ConclusionsHealth policy must establish systematic monitoring of the migrant HCWF including actor-centred approaches, support integration in destination countries as well as health system development in sending countries, and invest in evidence-based circular migration policy.
Do try this at home: Age prediction from sleep and meditation with large-scale low-cost mobile EEG
Authors: Banville Hubert , Jaoude Maurice Abou , Wood Sean U.N. , Aimone Chris , Holst Sebastian C. , Gramfort Alexandre , Engemann Denis-Alexander 
Published: April 2023

AbstractEEG is an established method for quantifying large-scale neuronal dynamics which enables diverse real-world biomedical applications including brain-computer interfaces, epilepsy monitoring and sleep staging. Advances in sensor technology have freed EEG from traditional laboratory settings, making low-cost ambulatory or at-home assessments of brain function possible. While ecologically valid brain assessments are becoming more practical, the impact of their reduced spatial resolution and susceptibility to noise remain to be investigated. This study set out to explore the potential of at-home EEG assessments for biomarker discovery using the brain age framework and four-channel consumer EEG data. We analyzed recordings from more than 5200 human subjects (18-81 years) during meditation and sleep, focusing on the age prediction task. With cross-validatedR2scores between 0.3 - 0.5, prediction performance was within the range of results obtained by recent benchmarks focused on laboratory-grade EEG. While age prediction was successful from both meditation and sleep recordings, the latter led to higher performance. Analysis by sleep stage uncovered that N2-N3 stages contained most of the signal. When combined, EEG features extracted from all sleep stages gave the best performance, suggesting that the entire night of sleep contains valuable age-related information. Furthermore, model comparisons suggested that information was spread out across electrodes and frequencies, supporting the use of multivariate modeling approaches. Thanks to our unique dataset of longitudinal repeat sessions spanning 153 to 529 days from eight subjects, we finally evaluated the variability of EEG-based age predictions, showing that they reflect both trait- and state-like information. Overall, our results demonstrate that state-of-the-art machine learning approaches based on age prediction can be readily applied to real-world EEG recordings obtained during at-home sleep and meditation practice.
WITHDRAWN: The adhesion GPCR Adgrd1 is a prion protein receptor and a mediator of prion cytotoxicity
Authors: Lakkaraju Asvin KK , Tejero Oliver , Guixà-González Ramon , Cecco Elena De , Jungo Martina , Tsai Ching-Ju , Mastromartino Rocco , Marino Jacopo , Deupi Xavier , Hornemann Simone , Schertler Gebhard FX , Aguzzi Adriano 
Published: April 2023

Withdrawal StatementThe authors have withdrawn their manuscript owing to several irregularities that have recently come to light. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Beyond resilience: towards antifragility?
Authors: Hillson David 
Published: April 2023

PurposeThis opinion piece draws on the author's experience as a thought leader and expert practitioner in risk management to explore possible routes to applying antifragility in the organisational context, drawing on three metaphors from outside the business domain. Organisational responses to stressors have focused on the development of robustness and resilience. Recent global events have highlighted weaknesses in both these approaches. Antifragility might prove to be a valuable addition to the organisational armoury, but little progress has been made in finding practical implementations of the concept since it was first proposed over 10 years ago (Taleb, 2012).Design/methodology/approachDistinctions between robustness, resilience and antifragility are clarified. Descriptive analogy is used to expose ways in which antifragility might be implemented in practice, by comparison with three disparate metaphors.FindingsAntifragility is currently not well understood or implemented, but it offers a potentially powerful additional organisational strategy in response to stress, to complement more traditional robustness and resilience approaches. Drawing on the three metaphors, four distinct types of antifragility are outlined which suggest how organisations might begin to develop antifragility in practice: innate antifragility, adaptive antifragility, rheopectic antifragility and emergent antifragility. These are presented as an organisational antifragility taxonomy that can support further research and practice.Originality/valueThe use of metaphor to explore antifragility is unique, providing insights into ways it might be applied.