bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do inoculated microbial consortia perform better than single strains in living soil? A meta-analysis
Authors: Liu Xipeng , Mei Siyu , Salles Joana Falcão 
Published: March 2023

AbstractMicrobial consortium inoculation has been proposed as a natural-based strategy to safeguard multiple ecosystem services. Still, its empirical effects and comparisons to single-species inoculation have yet to be systematically quantified. In this global meta-analysis of 51 live-soil studies, we compared the impact (mean and variability) of single-species and consortium inoculations on biofertilization and bioremediation. Our results showed that both single-species and consortium inoculations increased plant growth by 29% and 48%, respectively, and pollution remediation by 48% and 80%, respectively, compared with non-inoculated treatments. We revealed the potential mechanisms contributing to the effectiveness of consortium inoculation, which are associated with the diversity of inoculants and the synergistic effect between frequently used inoculums (e.g.,BacillusandPseudomonas). Despite a reduction in efficacy in field settings compared to greenhouse results, consortium inoculation had a more significant overall advantage under various conditions. We recommend increasing original soil organic matter, N, and P content and regulating soil pH to 6-7 to achieve a better inoculation effect. Overall, these findings support the use of microbial consortia for improved biofertilization and bioremediation in living soil and suggest perspectives for constructing and inoculating beneficial microbial consortia.
Norovirus MLKL-like pore forming protein initiates programed cell death for viral egress
Authors: Wang Guoxun , Zhang Di , Orchard Robert , Hancks Dustin C. , Reese Tiffany A. 
Published: March 2023

AbstractNon-enveloped viruses require cell lysis to release new virions from infected cells, suggesting that these viruses require mechanisms to induce cell death. Noroviruses are one such group of viruses, but a mechanism of norovirus-infection triggered cell death and lysis are unknown. Here we have identified a molecular mechanism of norovirus-induced cell death. We found that the norovirus-encoded NTPase contains a N-terminal four helix bundle domain homologous to the pore forming domain of the pseudokinase Mixed Lineage Kinase Domain-Like (MLKL). Norovirus NTPase acquired a mitochondrial localization signal, thereby inducing cell death by targeting mitochondria. NTPase full length (NTPase-FL) and N-terminal fragment (NTPase-NT) bound mitochondrial membrane lipid cardiolipin, permeabilized mitochondrial membrane and induced mitochondrial dysfunction. Both the N-terminal region and the mitochondrial localization motif of NTPase were essential for cell death, virus egress from cells and virus replication in mice. These findings suggest that noroviruses stole a MLKL-like pore forming domain and co-opted it to facilitate viral egress by inducing mitochondrial dysfunction.
Harnessing PROTAC technology to combat stress hormone receptor activation
Authors: Gazorpak Mahshid , Hugentobler Karina M. , Paul Dominique , Germain Pierre-Luc , Matthis Kei , Rudolf Remo , Barrenechea Sergio Mompart , Kretschmer Miriam , Fischer Vincent , Xue Xiaohan , Privitera Mattia , Ivanova Iryna , Hierlemann Andreas , Meijer Onno C. , Carreira Erick M. , Bohacek Johannes , Gapp Katharina 
Published: March 2023

AbstractCounteracting the overactivation of glucocorticoid receptors (GR) is an important therapeutic goal in stress-related psychiatry and beyond. The only clinically approved GR antagonist lacks selectivity and induces unwanted side effects. To complement existing tools of small-molecule-based inhibitors, we present a highly potent, novel catalytically-driven GR degrader, KH-103, based on proteolysis-targeting chimera technology. This selective degrader enables immediate and reversible GR depletion that is independent of genetic manipulation and circumvents transcriptional adaptations to inhibition. KH-103 achieves passive inhibition, preventing agonistic induction of gene expression, and significantly averts the GR’s genomic effects compared to two currently available inhibitors. Application in primary-neuron cultures revealed the dependency of a glucocorticoid-induced increase in spontaneous calcium activity on GR. Finally, we present a proof of concept for application in-vivo. KH-103 opens opportunities for a more lucid interpretation of GR functions with translational potential.
Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping
Authors: Foran Gregory , Hallam Ryan Douglas , Megaly Marvel , Turgambayeva Anel , Antfolk Daniel , Li Yifeng , Luca Vincent C. , Necakov Aleksandar 
Published: March 2023

AbstractThe Notch receptor is a pleiotropic signaling protein that translates intercellular ligand interactions into changes in gene expressionviathe nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNAin situ,Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD can form condensates that positively facilitate Notch target gene expression. We determined that N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins. We show that the capacity for condensation is due to the intrinsically disordered transcriptional activation domain of the N1ICD. In addition, the formation of such transcriptional condensates acts to promote Notch-mediated super enhancer-looping and concomitant activation of the MYC protooncogene expression. Overall, we introduce a novel mechanism of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into the assembly of transcriptional condensates that facilitate gene expression by enriching essential transcriptional machineries at target genomic loci.
Parallel genetic adaptation ofBacillus subtilisto different plant species
Authors: Hu Guohai , Wang Yue , Blake Christopher , Nordgaard Mathilde , Liu Xin , Wang Bo , Kovács Ákos T. 
Published: March 2023

AbstractPlant growth-promoting rhizobacteria benefit plants by stimulating their growth or protecting them against phytopathogens. Rhizobacteria must colonise and persist on plant roots to exert their benefits. However, little is known regarding the processes by which rhizobacteria adapt to different plant species, or behave under alternating host plant regimes. Here, we used experimental evolution and whole-population whole-genome sequencing to analyse howBacillus subtilisevolves onArabidopsis thalianaand tomato seedlings, and under an alternating host plant regime, in a static hydroponic setup. We observed parallel evolution across multiple levels of biological organisation in all conditions, which was greatest for the two heterogeneous, multi-resource spatially-structured environments at the genetic level. Species-specific adaptation at the genetic level was also observed, possibly caused by the selection stress imposed by different host plants. Furthermore, a trade-off between motility and biofilm development was supported by mutational changes in motility– and biofilm-related genes. Finally, we identified several condition-specific and common targeted genes in different environments by comparing three differentB. subtilisbiofilm adaptation settings. The results demonstrate a common evolutionary pattern whenB. subtilisis adapting to the plant rhizosphere in similar conditions, and reveal differences in genetic mechanisms between different host plants. These findings will likely support strain improvements for sustainable agriculture.Data summarySequencing data associated with this article are available in the CNGB Sequence Archive (CNSA) [1] of the China National GeneBank DataBase (CNGBdb) [2] under accession numbers CNP0002416 and CNP0003952. Strain data for the DK1042 ancestor are available under accession number CNP0002416.Impact statementFor rhizobacteria to benefit plant growth and protect against phytopathogens, bacteria must colonise and persist on plant roots. Understanding how rhizobacteria adapt to different plant species will assist strain development in sustainable agriculture. To explore the rhizobacterial adaptation process for different plant species and alternating host regimes,B. subtiliswas experimentally evolved onA. thalianaor tomato roots, or an alternating host regime. Both parallel and species-specific adaptation was revealed at the genetic level. Analysis of the trade-off between motility and biofilm formation revealed several condition-specific and commonly targeted genes based on experimentally evolvingB. subtilisbiofilms.
Adaptive Expression of Engrams by Retroactive Interference
Authors: Autore Livia , O’Leary James D. , Ortega-de San Luis Clara , Ryan Tomás J. 
Published: March 2023

SUMMARYLong-term memories are stored as stable configurations of neuronal ensembles, termed engrams. While investigation of engram cell properties and functionality in memory recall has been extensive, less is known about how engram cells are affected by forgetting. We describe a form of interference-based forgetting using an object memory behavioral paradigm. By using activity-dependent cell labelling, we show that although retroactive interference results in decreased engram cell reactivation during recall trials, optogenetic stimulation of the labelled engram cells is sufficient to induce memory retrieval. Forgotten engrams may also be reinstated via the presentation of similar or related environmental information. Furthermore, we demonstrate that engram activity is necessary for interference to occur. Taken together, these findings indicate that retroactive interference modulates engram expression in a manner that is both reversible and updatable. Retroactive inference may constitute a form of adaptive forgetting, where in everyday life new perceptual and environmental inputs modulate the natural forgetting process.
Novel in-silico predicted matrikines are differential mediators of in vitro and in vivo cellular metabolism
Authors: Jariwala Nathan , Ozols Matiss , Eckersley Alexander , Mambwe Bezaleel , Watson Rachel E B , Zeef Leo , Gilmore Andrew , Debelle Laurent , Bell Mike , Bradley Eleanor J , Doush Yegor , Courage Carole , Leroux Richard , Peschard Olivier , Mondon Philippe , Ringenbach Caroline , Bernard Laure , Pitois Aurelien , Sherratt Michael J 
Published: March 2023

SummaryThe exogenous application of small peptides can beneficially affect clinical skin appearance (wrinkles) and architecture (collagen and elastic fibre deposition and epidermal thickness). However, the discovery of new bioactive peptides has not been underpinned by any guiding hypothesis. As endogenous extracellular matrix (ECM)-derived peptides produced during tissue remodelling can act as molecular signals influencing cell metabolism, we hypothesised that protease cleavage site prediction could identify putative novel matrikines with beneficial activities. Here, we present anin silicotoin vivodiscovery pipeline, which enables the prediction and characterisation of peptide matrikines which differentially influence cellular metabolismin vitro. We use this pipeline to further characterise a combination of two novel ECM peptide mimics (GPKG and LSVD) which actin vitroto enhance the transcription of ECM organisation and cell proliferation genes andin vivoto promote epithelial and dermal remodelling. This pipeline approach can both identify new matrikines and provide insights into the mechanisms underpinning tissue homeostasis and repair.
Development of aPlasmodium vivaxbiobank for functionalex vivoassays
Authors: Dash Rashmi , Skillman Kristen M. , Pereira Ligia , Mascarenhas Anjali , Dass Sheena , Walke Jayashri , Almeida Anvily , Fernandes Mezia , Gomes Edwin , White John , Chery-Karschney Laura , Khandeparkar Anar , Rathod Pradipsinh K. , Duraisingh Manoj T. , Kanjee Usheer 
Published: March 2023

AbstractBackgroundPlasmodium vivaxis the second most prevalent cause of malaria yet remains challenging to study due to the lack of a continuousin vitroculture system, highlighting the need to establish a biobank of clinical isolates with multiple freezes per sample for use in functional assays. Different methods for cryopreserving parasite isolates were compared and subsequently the most promising one was validated. Enrichment of early- and late-stage parasites and parasite maturation were quantified to facilitate assay planning.MethodsIn order to compare cryopreservation protocols, nine clinicalP. vivaxisolates were frozen with four glycerolyte-based mixtures. Parasite recovery post thaw, post KCl-Percoll enrichment and in short-termin vitroculture was measured via slide microscopy. Enrichment of late-stage parasites by magnetic activated cell sorting (MACS) was measured. Short and long-term storage of parasites at either -80°C or liquid nitrogen were also compared.ResultsOf the four cryopreservation mixtures, one mixture (glycerolyte:serum:RBC at a 2.5:1.5:1 ratio) resulted in improved parasite recovery and statistically significant (P<0.05) enhancement in parasite survival in short-termin vitroculture. A parasite biobank was subsequently generated using this protocol resulting in a collection with 106 clinical isolates, each with 8 vials. The quality of the biobank was validated by measuring several factors from 47 thaws: the average reduction in parasitemia post-thaw (25.3%); the average fold enrichment post KCl-Percoll (6.65-fold); and the average percent recovery of parasites (22.0%, measured from 30 isolates). During short-termin vitroculture, robust maturation of ring stage parasites to later stages (>20% trophozoites, schizonts and gametocytes) was observed in 60.0% of isolates by 48 hours. Enrichment of mature parasite stages via MACS showed good reproducibility, with an average 30.0% post-MACS parasitemia and an average 5.30 × 105parasites/vial. Finally, the effect of storage temperature was tested, and no large impacts from short-term (7 day) or long term (7 – 10 year) storage at -80°C on parasite recovery, enrichment or viability was observed.ConclusionsHere, an optimized freezing method forP. vivaxclinical isolates is demonstrated as a template for the generation and validation of a parasite biobank for use in functional assays.
Multifaceted luminance gain control beyond photoreceptors inDrosophila
Authors: Ketkar Madhura D. , Shao Shuai , Gjorgjieva Julijana , Silies Marion 
Published: March 2023

AbstractAnimals navigating in natural environments must handle vast changes in their sensory input. Visual systems, for example, handle changes in luminance at many timescales, from slow changes across the day to rapid changes during active behavior. To maintain luminance-invariant perception, visual systems must adapt their sensitivity to changing luminance at different timescales. We demonstrate that luminance gain control in photoreceptors alone is insufficient to explain luminance invariance at both fast and slow timescales and reveal the algorithms that adjust gain past photoreceptors in the fly eye. We combined imaging and behavioral experiments with computational modeling to show that, downstream of photoreceptors, circuitry taking input from the single luminance-sensitive neuron type L3 implements gain control at fast and slow timescales. This computation is bidirectional in that it prevents underestimation of contrasts in low luminance and overestimation in high luminance. An algorithmic model disentangles these multifaceted contributions and shows that the bidirectional gain control occurs at both timescales. The model implements a nonlinear interaction of luminance and contrast to achieve gain correction at fast timescales and a dark-sensitive channel to improve the detection of dim stimuli at slow timescales. Together, our work demonstrates how a single neuronal channel performs diverse computations to implement gain control at multiple timescales that are together important for navigation in natural environments.Significance StatementLuminance varies slowly throughout the day, or rapidly during movements. Yet, animals show luminance-invariant behaviors to visual cues across these scenarios. Combining in vivo imaging, behavioral analyses and computational modeling, we here show that diverse luminance gain control operations required for robust visual processing exist in the fly visual circuitry beyond photoreceptors. Despite relying on a single luminance-sensitive neuron type, this luminance gain control is multifaceted, in that it achieves both gain increments and decrements at two different timescales. Overall, the study sheds light on a circuit gain control strategy operating at multiple timescales, which together challenge luminance-invariant visual behaviors in natural environments.
Polθ is phosphorylated by Polo-like kinase 1 (PLK1) to enable repair of DNA double strand breaks in mitosis
Authors: Gelot Camille , Kovacs Marton Tibor , Miron Simona , Mylne Emilie , Ghouil Rania , Popova Tatiana , Dingli Florent , Loew Damarys , Guirouilh-Barbat Josée , Del Nery Elaine , Zinn-Justin Sophie , Ceccaldi Raphael 
Published: March 2023

AbstractDNA double strand breaks (DSBs) are deleterious lesions that challenge genome integrity. To mitigate this threat, human cells rely on the activity of multiple DNA repair machineries that are tightly regulated throughout the cell cycle1. In interphase, DSBs are mainly repaired by non-homologous end joining (NHEJ) and homologous recombination (HR)2. However, these pathways are completely inhibited in mitosis3–5, leaving the fate of mitotic DSBs unknown. Here we show that DNA polymerase theta (Polθ)6repairs mitotic DSBs and thereby maintains genome integrity. In contrast to other DSB repair factors, Polθ function is activated in mitosis upon phosphorylation by the Polo-like kinase 1 (PLK1). Phosphorylated Polθ is recruited to mitotic DSBs, where it mediates joining of broken DNA ends, while halting mitotic progression. The lack of Polθ leads to a shortening of mitotic duration and defective repair of mitotic DSBs, resulting in a loss of genome integrity. In addition, we identify mitotic Polθ repair as the underlying cause of the synthetic lethality between Polθ and HR. Our findings reveal the critical importance of mitotic DSB repair for maintaining genome stability.
Secondary bile acid production by gut bacteria promotes Western diet-associated colorectal cancer
Authors: Wortmann Esther , Osswald Annika , Wylensek David , Kuhls Stephanie , Coleman Olivia I. , Ducarmon Quinten , Liang Wei , Treichel Nicole , Schumacher Fabian , Volet Colin , Matysik Silke , Kleigrewe Karin , Gigl Michael , Rohn Sascha , Kleuser Burkhard , Liebisch Gerhard , Schnieke Angelika , Bernier-Latmani Rizlan , Zeller Georg , Haller Dirk , Flisikowski Krzysztof , Ocvirk Soeren , Clavel Thomas 
Published: March 2023

AbstractWestern diet is an important risk factor for the development of sporadic colorectal cancer (CRC). Dietary fat stimulates bile acid (BA) production by the host and their conversion to secondary BAs by 7α-dehydroxylating (7αDH+) bacteria, but causal proof of their tumor-promoting effectsin vivois lacking. To address this, we performed feeding studies in a genetically engineered pig model of CRC combined with multi-omics analyses and gnotobiotic mouse studies. Western diet worsened the disease phenotype inAPC1311/+pigs. This was accompanied by microbiota changes, increased levels of the secondary bile acid deoxycholic acid (DCA), and higher colonic epithelial cell proliferation. The latter was counteracted by using the BA-scavenging drug colestyramine. Metagenomic analysis across multiple cohorts revealed higher occurrence ofbai(BA inducible) operons fromClostridium scindensand close relatives in stool of CRC subjects (n = 1,034). Using two gnotobiotic mouse models of CRC, we demonstrate that colonization with 7αDH+ bacteria (C. scindensorExtibacter muris) increased colonic tumor loads. This work provides clear evidence for the causal role of microbiome-derived DCA production in CRC under detrimental dietary conditions, opening avenues for future preventive strategies.
High-level cognition is supported by information-rich but compressible brain activity patterns
Authors: Owen Lucy L. W. , Manning Jeremy R. 
Published: March 2023

AbstractBrain activity patterns are highly flexible and often complex, but also highly structured. Here we examined how fundamental properties of brain activity patterns relate to ongoing cognitive processes. To this end, we applied dimensionality reduction algorithms and pattern classifiers to functional neuroimaging data collected as participants listened to a story, temporally scrambled versions of the story, or underwent a resting state scanning session. These experimental conditions were intended to require different depths of processing and inspire different levels of cognitive engagement. We considered two primary aspects of the data. First, we treated the maximum achievable decoding accuracy across participants as an indicator of the “informativeness” of the recorded patterns. Second, we treated the number of features (components) required to achieve a threshold decoding accuracy as a proxy for the “compressibility” of the neural patterns (where fewer components indicate greater compression). Overall, we found that the peak decoding accuracy (achievable without restricting the numbers of features) was highest in the intact (unscrambled) story listening condition. However, the number of features required to achieve comparable classification accuracy was also lowest in the intact story listening condition. Taken together, our work suggests that our brain networks flexibly reconfigure according to ongoing task demands, and that the activity patterns associated with higher-order cognition and high engagement are both more informative and more compressible than the activity patterns associated with lower-order tasks and lower levels of engagement.Significance StatementHow our brains respond to ongoing experiences depends on what we are doing and thinking about, among other factors. To study how brain activity reflects ongoing cognition, we examined two fundamental aspects of brain activity under different cognitive circumstances: informativeness and compressibility. Informativeness refers to the extent to which brain patterns are both temporally specific and consistent across different people. Compressibility refers to how robust the informativeness of brain patterns is to dimensionality reduction. Brain activity evoked by higher-level cognitive tasks are both more informativeandmore compressible than activity evoked by lower-level tasks. Our findings suggest that our brains flexibly reconfigure themselves to optimize different aspects of how they function according to ongoing cognitive demands.