bluuebunny/crossref_metadata_2025_split huggingface dataset:
SlS5H silencing reveals specific pathogen-triggered salicylic acid metabolism in tomato
Authors: Payá C , Minguillón S , Hernández M , Miguel SM , Campos L , Rodrigo I , Bellés JM , López-Gresa MP , Lisón P 
Published: March 2022

ABSTRACTThe phytohormone salicylic acid (SA or 2-hydroxybenzoic acid) plays an important role in plant biotic and abiotic responses. Gentisic acid (GA or 2,5-Dihydroxybenzoic acid, 2,5-DHBA) is the product of the SA 5-hydroxylation which is catalysed by the S5H enzyme, also known as DMR6. GA has been described to accumulate at high levels in compatible plant-pathogen interactions such as tomato plants infected by Citrus Exocortis Viroid (CEVd), and to a much lesser extend upon Pseudomonas syringae DC3000 pv. tomato (Pst) infection. Here we describe the specific effect that tomato SlS5H impairment produces on both plant-pathogen interactions. The induction of SlS5H in tomato plants by different pathogens was corroborated by qRT-PCR and correlated with previously described 2,5-DHBA accumulations. Transient SlS5H over-expression assays in Nicotiana benthamiana confirmed that SA is a substrate for SlS5H in vivo. RNAi_SlS5H tomato transgenic plants were generated and characterized upon CEVd and Pst infections. Transgenic tomato plants displayed an activation of defences and therefore a loss of susceptibility against both pathogens, and alternative SA homeostasis seems to occur for each specific interaction. Metabolomic assays revealed that whilst the glycosylated form of SA was the most discriminant metabolite found in CEVd infected RNAi_SlS5H transgenic plants, trans-feruloyldopamine, feruloylquinic acid, feruloylgalactarate and 2-hydroxyglutarate were the most accumulated compounds in the Pst-infected transgenic tomato leaves. Transgenic lines also displayed hyper susceptibility to Botrytis cinerea, as well as a smaller size and early senescence. Collectively, our results reveal a novel mechanism by which tomato plants specifically set SA homeostasis upon different pathogen attacks.One sentence summaryThe impairment of SA hydroxylation in tomato plants uncovers specific SA homeostasis upon CEVd or Pseudomonas syringae infections.
Beyond pulsed inhibition: Alpha oscillations modulate attenuation and amplification of neural activity in the awake resting-state
Authors: Lombardi Fabrizio , Herrmann Hans J. , Parrino Liborio , Plenz Dietmar , Scarpetta Silvia , Vaudano Anna Elisabetta , de Arcangelis Lucilla , Shriki Oren 
Published: March 2022

AbstractThe alpha rhythm is a distinctive feature of the awake resting-state of the human brain. Recent evidence suggests that alpha plays an active role in information processing, modulating behavioral and cognitive performance. However, the functional role of alpha oscillations in the resting-state neuronal dynamics remains poorly understood. To address this question, we investigate collective neural activity during resting wake and NREM sleep, a physiologic state with marginal presence of alpha rhythm. We show that, during resting wake, alpha oscillations drive an alternation of attenuation and amplification bouts in neural activity. Our analysis indicates that inhibition is activated in pulses that last a single alpha cycle and gradually suppress neural activity, while excitation is successively enhanced over timescales of a few alpha cycles to amplify neural activity. Furthermore, we show that long-term, intermittent fluctuations in alpha amplitude—known as the “waxing and waning” phenomenon—are associated with an attenuation-amplification mechanism acting over the timescales of several seconds and described by a power law decay of the activity rate in the “waning” phase. Importantly, we do not observe such dynamics during NREM sleep. The results suggest that the alpha rhythm acts as a “pacemaker” for the alternation of inhibition and excitation bouts across multiple timescales, the “waxing and waning” being a long-term control mechanism of cortical excitability. The amplification regime observed beyond the timescales of the individual alpha cycle suggests in turn that alpha oscillations might modulate the intensity of neural activity not only through pulses of inhibition, as proposed in the pulsed inhibition hypothesis, but also by timely enhancing excitation (or dis-inhibition).
What are oxytocin assays measuring? Epitope mapping, metabolites, and comparisons of wildtype & knockout mouse urine
Authors: Gnanadesikan Gitanjali E. , Hammock Elizabeth A.D. , Tecot Stacey R. , Lewis Rebecca J. , Hart Russ , Carter C. Sue , MacLean Evan L. 
Published: March 2022

AbstractOxytocin has become a popular analyte in behavioral endocrinology in recent years, due in part to its roles in social behavior, stress physiology, and cognition. Urine samples have the advantage of being non-invasive and minimally disruptive to collect, allowing for oxytocin measurements even in some wild populations. However, methods for urinary oxytocin immunoassay have not been sufficiently optimized and rigorously assessed for their potential limitations. Using samples from oxytocin knockout (KO) and wildtype (WT) mice, we find evidence of considerable interference in unextracted urine samples, with similar distributions of measured oxytocin in both genotypes. Importantly, although this interference can be reduced by a reversed-phase solid-phase extraction (SPE), this common approach is not sufficient for eliminating false-positive signal on three immunoassay kits. To better understand the source of the observed interference, we conducted epitope mapping of the Arbor Assays antibody and assessed its cross-reactivity with known, biologically active fragments of oxytocin. We found considerable cross-reactivity (0.5-52% by-molarity) for three fragments of oxytocin that share the core epitope, with more cross-reactivity for longer fragments. Given the presence of some cross-reactivity for even the tripeptide MIF-1, it is likely that many small protein metabolites might be sufficiently similar to the epitope that at high concentrations they interfere with immunoassays. We present a new mixed-mode cation-exchange SPE method that minimizes interference—with knockout samples measuring below the assay’s limit of detection—while effectively retaining oxytocin from the urine of wildtype mice. This method demonstrates good parallelism and spike recovery across multiple species (mice, dogs, sifakas, humans). Our results suggest that immunoassays of urine samples may be particularly susceptible to interference, even when using common extraction protocols, but that this interference can be successfully managed using a novel mixed-mode cation exchange extraction.
De-heterogeneity of the eukaryotic viral reference database (EVRD) improves the accuracy and efficiency of viromic analysis
Authors: Chen Junjie , Yan Xiaomin , Sun Yue , Ren Zilin , Yan Guangzhi , Wang Guoshuai , Liu Yuhang , Zhao Zihan , Liu Yang , Tu Changchun , He Biao 
Published: March 2022

AbstractWidespread in public databases, the notorious contamination in virus reference databases often leads to confusing even wrong conclusions in applications like viral disease diagnosis and viromic analysis, highlighting the need of a high-quality database. Here, we report the comprehensive scrutiny and the purification of the largest viral sequence collections of GenBank and UniProt by detection and characterization of heterogeneous sequences (HGSs). A total of 766 nucleotide- and 276 amino acid-HGSs were determined with length up to 6,605 bp, which were widely distributed in 39 families, with many involving highly public health-related viruses, such as hepatitis C virus, Crimea-Congo hemorrhagic fever virus and filovirus. Majority of these HGSs are sequences of a wide range of hosts including humans, with the rest resulting from vectors, misclassification and laboratory components. However, these HGSs cannot be simply considered as exotic contaminants, since part of which are resultants of natural occurrence or artificial engineering of the viruses. Nevertheless, they significantly disturb the genomic analysis, and hence were deleted from the database. A further augmentation was implemented with addition of the risk and vaccine sequences, which finally results in a high-quality eukaryotic virus reference database (EVRD). EVRD showed higher accuracy and less time-consuming without coverage compromise by reducing false positives than other integrated databases in viromic analysis. EVRD is freely accessible with favorable application in viral disease diagnosis, taxonomic clustering, viromic analysis and novel virus detection.
A cell non-autonomous FOXO/DAF-16-mediated germline quality assurance program that responds to somatic DNA damage
Authors: Sarkar Gautam Chandra , Rautela Umanshi , Goyala Anita , Datta Sudeshna , Anand Nikhita , Singh Anupama , Singh Prachi , Chamoli Manish , Mukhopadhyay Arnab 
Published: March 2022

AbstractGermline integrity is critical for progeny fitness. Organisms deploy the DNA damage response (DDR) signalling to protect germline from genotoxic stress, facilitating cell-cycle arrest of germ cells and DNA repair or their apoptosis. Cell-autonomous regulation of germline quality is well-studied; however, how quality is enforced cell non-autonomously on sensing somatic DNA damage is less known. Using Caenorhabditis elegans, we show that DDR disruption, only in the uterus, when insulin-IGF-1 signalling (IIS) is low, arrests germline development and induces sterility in a FOXO/DAF-16 transcription factor (TF)-dependent manner. Without FOXO/DAF-16, germ cells of the IIS mutant escape arrest to produce poor quality oocytes, showing that the TF imposes strict quality control during low IIS. In response to low IIS in neurons, FOXO/DAF-16 works cell autonomously as well as non-autonomously to facilitate the arrest. Activated FOXO/DAF-16 promotes transcription of checkpoint and DDR genes, protecting germline integrity. However, on reducing DDR during low IIS, the TF decreases ERK/MPK-1 signaling below a threshold, and transcriptionally downregulates genes involved in spermatogenesis-to-oogenesis switch as well as cdk-1/Cyclin B to promote germline arrest. Altogether, our study reveals how cell non-autonomous function of FOXO/DAF-16 promotes germline quality and progeny fitness in response to somatic DNA damage.Significance StatementReproductive decisions are supervised processes that take into account various inputs like cellular energy availability and status of damage repair in order to ensure healthy progeny. In this study, we show that the absence of optimal DNA damage repair in the somatic uterine tissues prevents oocyte development by the cell-autonomous as well non-autonomous function of activated FOXO transcription factor DAF-16. Thus, this study elucidates a new surveillance role of FOXO/DAF-16 in somatic tissues that ensures progeny fitness.
CDK4 deletion in mice prevents fat accumulation and increases endurance capacity through activation of estrogen-related receptor (ERR)-driven oxidative metabolism in skeletal muscle
Authors: Barquissau Valentin , Zanou Nadège , Geller Sarah , Castillo-Armengol Judit , Marzetta Flavia , Huber Katharina , Ziegler Dorian , Lopez-Mejia Isabel , Fernandez Joan Blanco , Roger Catherine , Guex Nicolas , Preitner Frédéric , Vanacker Jean-Marc , Fajas Lluis 
Published: March 2022

AbstractCyclin-dependent kinase 4 (CDK4) canonical role is to control cell cycle progression from G1 to S phases. However, recent studies reported that CDK4 regulates energy metabolism in non-proliferating cells such as hepatocytes or adipocytes. The objective of our work is to study CDK4 function in skeletal muscle using a model of mice lacking CDK4 (cdk4-/-). By coupling treadmill running to indirect calorimetry, we show thatcdk4-/-mice display improved endurance and higher capacity to use fat as fuel during exercise. Isolated muscles lacking CDK4 are more resistant to fatigue in response to repeated contractions and have increased oxidative capacity and mitochondrial content compared tocdk4+/+muscles. Transcriptomic analysis reveals upregulation of genes controlled by the nuclear receptors estrogen-related receptors (ERRs) incdk4-/-skeletal muscle, associated with elevated levels of the ERR co-activator PGC1a. Supporting in vivo results, C2C12 myotubes treated with a CDK4 inhibitor have increased mitochondrial oxygen consumption, PGC1α expression and ERR transcriptional activity measured by a luciferase reporter. In normal housing conditions,cdk4-/-mice show an increased basal metabolic rate and are resistant to weight gain and fat accumulation. In conclusion, our study uncovers a role for CDK4 in the control of skeletal muscle metabolism. Moreover, CDK4 inhibition may be an alternative strategy against obesity-associated metabolic disorders.
Collagen-VI expression is negatively mechanosensitive in pancreatic cancer cells and supports the metastatic niche
Authors: Papalazarou Vasileios , Drew James , Juin Amelie , Spence Heather J. , Nixon Colin , Salmeron-Sanchez Manuel , Machesky Laura M. 
Published: March 2022

AbstractPancreatic cancer is a deadly disease with high rates of metastasis, though how tumor cells establish metastatic lesions is not fully understood. A key feature of primary pancreatic tumors is extensive fibrosis due to deposition of extracellular matrix. While pancreatic cancer cells are programmed by stimuli derived from a stiff ECM, metastasis requires loss of attachment as well as adaptation to a softer microenvironment upon reaching distant sites. Growing evidence suggests that stiff ECM influences pancreatic cancer cell behaviour. Here we argue that this influence is reversible and that pancreatic cancer cells can be reprogrammed upon sensing of soft substrates. Through use of engineered polyacrylamide hydrogels with tuneable mechanical properties, we show that Collagen-VI is specifically upregulated on soft substrates, due to a lack of integrin engagement and low YAP1 activity. Collagen-VI supports migration in vitro and metastasis formation in vivo. Metastatic nodules formed by pancreatic cancer cells lacking Col6a1 expression, were characterised by stromal cell-derived collagen-VI deposition, suggesting that collagen-VI, either cancer or stroma derived, is an essential component of the metastatic niche.Summary StatementCollagen-VI is expressed by pancreatic tumors and metastases in a mechanosensitive way to promote niche colonisation.
A tissue boundary orchestrates the segregation of inner ear sensory organs
Authors: Chen Ziqi , Żak Magdalena , Xu Shuting , de Andrés Javier , Daudet Nicolas 
Published: March 2022

AbstractThe inner ear contains distinct sensory organs, produced sequentially by segregation from a large sensory-competent domain in the developing otic vesicle. To understand the mechanistic basis of this process, we investigated the changes in prosensory cell patterning, proliferation and character during the segregation of some of the vestibular organs in the mouse and chicken otic vesicle. We discovered a specialized boundary domain, located at the interface of segregating organs. It is composed of prosensory cells that gradually enlarge, elongate and are ultimately diverted from a prosensory fate. Strikingly, the boundary cells align their apical borders and constrict basally at the interface of cells expressing or not the Lmx1a transcription factor, an orthologue of drosophila Apterous. The boundary domain is absent inLmx1a-deficient mice, which exhibit defects in sensory organ segregation, and is disrupted by the inhibition of ROCK-dependent actomyosin contractility. Altogether, our results suggest that actomyosin-dependent tissue boundaries ensure the proper separation of inner ear sensory organs and uncover striking homologies between this process and the compartmentalization of the drosophila wing disc by lineage-restricted boundaries.
GTEM cell design for controlled exposure to electromagnetic fields in biological system
Authors: Tao J. , Li Z.-G. , Vuong T.-H. , Kunduzova O. 
Published: March 2022

AbstractThis study describes a structure design of the Gigaherz Transverse Electromagnetic (GTEM) cell for electromagnetic tests in biological systems. Using electromagnetic simulation software we show that the optimization of final structure assures the criteria imposed on a low level of reflection towards the radio frequency generator, and a fairly uniform field in the test zone. A sensitivity study was also conducted when the cell was loaded with a few samples under test. We report that the level of reflection remains adequate as long as the test volume remains limited in relation to the size of the cell. The first estimation results on the SAR values are consistent with the distribution of the fields in the cell. A cell was fabricated with the design data, and tested for the reflection level. The measurements confirm the results of simulations.
A mechanistic spatiotemporal model for drug resistant infections
Authors: Lee Tamsin E. , De Salazar Pablo M. 
Published: March 2022

AbstractEffective public health strategies for preventing infectious diseases require a deep understanding of transmission dynamics. However, epidemiological data alone is often insufficient for guiding public health action, as transmission patterns emerge from complex human-environment interactions. Additionally, collecting empirical data is frequently limited by cost and logistical challenges, especially in low-resource settings. Consequently, health policy increasingly relies on inference models that account for spatial and temporal dimensions, confounding factors, and uncertainty.In this work, we introduce a novel hierarchical mechanistic Bayesian model based on ecological diffusion to improve epidemiological inference for spreading pathogens. This model is specifically designed to reveal underlying spatiotemporal dynamics from empirical data, explicitly accounting for sampling bias and uncertainty. To demonstrate its effectiveness, we apply the model to simulated data of a drug-resistant pathogen and formally compare its performance to state-of-the-art epidemiological regression models.Our findings show that the model accurately identifies transmission patterns and is particularly effective at pinpointing transmission hotspots and predicting spread pathways—critical capabilities for controlling drug-resistant pathogens. While reliable monitoring remains challenging in low-resource environments, this model addresses demographic sampling bias and spatiotemporal complexities, though concentrated sampling in presumed high-risk areas can sometimes distort transmission insights.The proposed framework can inform targeted public health interventions in the early stages of resistance emergence, offering valuable guidance for resource-constrained settings.
Unruly octopuses are the rule: Octopus vulgaris use multiple and individually variable strategies in an episodic-like memory task
Authors: Lisa Poncet , Coraline Desnous , Cécile Bellanger , Christelle Jozet-Alves 
Published: March 2022

AbstractThe evolution of complex cognition can be explained by different hypotheses, mutually non-exclusive: the social intelligence hypothesis, the ecological intelligence hypothesis and the predator-prey interaction hypothesis. Episodic-like memory can be used as a proxy to study complex cognition. This ability has mainly been studied through experimental tasks where subjects have to remember what they ate, where and when or in which context. Seemingly quite common in mammals and corvids, episodic-like memory abilities have been observed in only one invertebrate species: the common cuttlefish, a cephalopod mollusc. To explore if this ability is common to all cephalopods or if it has emerged to face specific constraints, we conducted an episodic-like memory task with seven Octopus vulgaris. Only one individual learnt the replenishing rates during the training and subsequently showed episodic-like memory abilities, whereas the other individuals favoured simpler foraging strategies, such as avoidance of familiarity and alternation, use of win-stay strategy and risk-sensitivity. A high variability in the use of these strategies was observed between and within individuals throughout the training. Since octopuses seem to live under lighter environmental pressure than cuttlefish, they may not need to rely on episodic-like memory abilities to optimize foraging as cuttlefish do. These results highlight the differences in the use of complex cognitive abilities between cuttlefish and octopuses, which might be linked with different environmental, predatory and social constraints.Summary statementWhen trained in an episodic-like memory task, common octopuses favour individually variable foraging strategies rather than keeping track of time to solve the task as cuttlefish do.
TENT2, TUT4, and TUT7 selectively regulate miRNA sequence and abundance
Authors: Yang Acong , Ros Xavier Bofill-De , Stanton Ryan , Shao Tie-Juan , Villanueva Patricia , Gu Shuo 
Published: March 2022

AbstractTENTs generate miRNA isoforms by 3’ tailing. However, little is known about how tailing regulates miRNA function. Here, we generated isogenic HEK293T cell lines in which TENT2, TUT4 and TUT7 were knocked out individually or in combination. Together with rescue experiments, we characterized TENT-specific effects by deep sequencing, Northern blot andin vitroassays. We found that 3’ tailing is not random but highly specific. In addition to its known adenylation, TENT2 contributes to guanylation and uridylation on mature miRNAs. TUT4 uridylates most miRNAs whereas TUT7 is dispensable. Removing adenylation has a marginal impact on miRNA levels. By contrast, abolishing uridylation leads to dysregulation of a set of miRNAs. Besides let-7, miR-181b and miR-222 are negatively regulated by TUT4/7 via distinct mechanisms while the miR-888 cluster is upregulated specifically by TUT7. Our results uncover the selective actions of TENTs in generating 3’ isomiRs and pave the way to investigate their functions.
Monomodular Pseudomonas aeruginosa phage JG004 lysozyme (Pae87) contains a bacterial surface-active antimicrobial peptide-like region and a possible substrate-binding subdomain
Authors: Vázquez Roberto , Seoane-Blanco Mateo , Rivero-Buceta Virginia , Ruiz Susana , van Raaij Mark J. , García Pedro 
Published: March 2022

Phage lysins are a source of novel antimicrobials to tackle the bacterial antibiotic-resistance crisis. The engineering of phage lysins is being explored as a game-changing technological strategy to introduce a more precise approach in the way in which antimicrobial therapy is applied. Such engineering efforts will benefit from a better understanding of lysin structure and function. In this work, the antimicrobial activity of the endolysin from Pseudomonas aeruginosa phage JG004, termed Pae87, has been characterized. This lysin had previously been identified as an antimicrobial agent candidate that is able to interact with the Gram-negative surface and disrupt it. Further evidence is provided here based on a structural and biochemical study. A high-resolution crystal structure of Pae87 complexed with a peptidoglycan fragment showed a separate substrate-binding region within the catalytic domain, 18 Å away from the catalytic site and located on the opposite side of the lysin molecule. This substrate-binding region was conserved among phylogenetically related lysins lacking an additional cell-wall-binding domain, but not among those containing such a module. Two glutamic acids were identified to be relevant for the peptidoglycan-degradation activity, although the antimicrobial activity of Pae87 was seemingly unrelated. In contrast, an antimicrobial peptide-like region within the Pae87 C-terminus, named P87, was found to be able to actively disturb the outer membrane and display antibacterial activity by itself. Therefore, an antimicrobial mechanism for Pae87 is proposed in which the P87 peptide plays the role of binding to the outer membrane and disrupting the cell-wall function, either with or without the participation of the catalytic activity of Pae87.