bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting GFPT2 to reinvigorate immunotherapy in EGFR-mutated NSCLC
Authors: Ao Luyao , Jia Wenjing , Gong Qixing , Cui Jiawen , Wang Jun , Yu Ying , Fu Chenghao , Li Haobin , Wei Jia , Wang Ruiqi , Wang Feiyi , Shang Xin , Li Yantong , Fang Shencun , Wang Guangji , Zhou Fang , Liu Jiali 
Published: March 2024

AbstractIn the evolving field of cancer immunotherapy, EGFR-mutated NSCLC presents a significant challenge, demonstrating marked innate resistance to established treatments. An effective method to counter this resistance remains elusive. Through comprehensive genetic and pharmacological analyses across various models, we have identified glutamine fructose-6-phosphate transaminase 2 (GFPT2) as a key facilitator of immune evasion in EGFR-mutated NSCLC. Mechanistically, under EGFR mutation condition, GFPT2 expression, which is typically low in normal tissues, is highly induced via EGFR/IRE1α/Xbp1s signaling axis, leading to a significant increase in intracellular UDP-GlcNAc and consequently, an altered N-glycosylation profile. GFPT2 escalates the expression and glycosylation of PD-L1, PVR and CD276, bolstering their interactions with CD8+T cells, and amplifies CD73 glycosylation, thereby intensifying adenosine-mediated CD8+T cells suppression. These actions collectively reduce tumor cell vulnerability to CD8+T cell-mediated death. Moreover, GFPT2 regulates EGFR glycosylation, which consequentially modulates the EGFR-dependent secretion of CXCL10 and VEGF, thus impeding CD8+T cell infiltration within tumors. We further identified a GFPT2 isoform-specific inhibitor that potentiates PD-1 blockade therapy beyond that of existing strategy, corroborated by results in xenografts and patient-derived organoids. Together, these findings illuminate the promising therapeutic potential of GFPT2 as a metabolic checkpoint, offering an innovative approach to invigorate immunotherapy in NSCLC with EGFR mutations.
A locally administered single cycle influenza vaccine expressing a non-fusogenic stabilised haemagglutinin stimulates strong T-cell and neutralising antibody immunity
Authors: Sadler Holly L. , Rijal Pramila , Tan Tiong Kit , Townsend Alain R. M. 
Published: March 2024

AbstractCurrent influenza vaccination approaches protect against specific viral strains, but do not consistently induce broad and long-lasting protection to the diversity of circulating influenza viruses. Single cycle viruses delivered to the respiratory tract may offer a promising solution as they safely express a diverse array of viral antigens by undergoing just one round of cell infection in their host and stimulate broadly protective resident memory T-cell responses in the lung. We have previously developed a vaccine candidate called S-FLU that is limited to a single cycle of infection by inactivation of the hemagglutinin signal sequence and induces a broadly cross-reactive T-cell response and antibodies to neuraminidase, but fails to induce neutralising antibodies to hemagglutinin after intranasal administration.This study describes the development of CLEARFLU, a derivative of S-FLU that is designed to add a neutralising antibody response to hemagglutinin. In contrast to S-FLU, which does not express a hemagglutinin molecule at the infected cell surface, CLEARFLU viruses express a stabilised non-fusogenic hemagglutinin. They are equally limited to a single cycle of infection, but induce a neutralising antibody response to the expressed hemagglutinin in addition to the cytotoxic T lymphocyte (CTL) responses to internal proteins and antibodies to neuraminidase induced by S-FLU. This represents a notable advantage as CLEARFLU viruses may provide sterile immunity against strain-matched challenge as well as non-sterile protection against a broad range of influenza viruses.ImportanceInfluenza is a serious public health concern, causing seasonal epidemics as well as pandemics in people. Influenza can also cause severe agricultural losses due to its circulation in farmed poultry and swine. A major challenge in the control of influenza is the diversity of circulating viruses. Developing vaccines which stimulate immunity to a wide array of influenza viruses is therefore important for protecting human and animal populations from disease and death. In this study, we describe an approach for developing influenza vaccines which trigger immune mechanisms shown to induce broad protection against a diversity of viruses, while also conserving the strong protection against specific strains observed in existing vaccines.
Genotypic and phenotypic characterization of a nosocomial outbreak ofCandida aurisin Spain during five years
Authors: Mulet-Bayona Juan Vicente , Cancino-Muñoz Irving , Salvador-García Carme , Tormo-Palop Nuria , Guna Remedios , González-Candelas Fernando , Gimeno-Cardona Concepción 
Published: March 2024

AbstractObjectivesThe investigation ofCandida aurisoutbreaks is needed to provide insights into its population structure and transmission dynamics. We genotypically and phenotypically characterized aC. aurisnosocomial outbreak occurred at the Consorcio Hospital General Universitario de Valencia (CHGUV), Spain.MethodsData and isolates were collected at CHGUV from September 2017 (first case) until September 2021. Thirty-five isolates, one from an environmental source, were selected for whole genome sequencing (WGS), and the genomes were analyzed along with 335 publicly available genomes, assigning them to one of the five major clades. In order to identify polymorphisms associated with drug resistance, we used the fully susceptible GCA_003014415.1 strain as reference sequence. Known mutations in geneserg11andfks1conferring resistance to fluconazole and echinocandins, respectively, were investigated. Isolates were classified into aggregating or non-aggregating.ResultsAll isolates belonged to clade III and were from an outbreak with a single origin. They clustered close to 3 publicly available genomes from a hospital from where the first patient was transferred, being the probable origin. The mutation VF125AL in theERG11protein, conferring resistance to fluconazole, was present in all the isolates and one isolate also carried the mutation S639Y in theFKS1protein. All the isolates had a non-aggregating phenotype.ConclusionsIsolates are genotypically related and phenotypically identical but one with resistance to echinocandins, which seems to indicate that they all belong to an outbreak originated from a single isolate, remaining largely invariable over the years. This result stresses the importance of implementing infection control practices as soon as the first case is detected or when a patient is transferred from a setting with known cases.
α7 nicotinic acetylcholine receptors are necessary for basal forebrain activation to increase expression of the nerve growth factor receptor TrkA
Authors: Kumro Jacob , Tripathi Ashutosh , Terry Alvin V. , Pillai Anilkumar , Blake David T 
Published: March 2024

AbstractActivation of the basal forebrain leads to increases in the expression of the nerve growth factor receptor, Tropomyosin receptor kinase A (TrkA) and decreases in expression of the beta amyloid cleavage enzyme 1 (BACE1) in the cerebral cortex of both sexes of 5xFAD mice. The studies described in this report were designed to determine if these changes were dependent on acetylcholine receptors. Mice were stimulated unilaterally in the basal forebrain for two weeks. Animals were administered a cholinergic antagonist, or saline, 30 minutes prior to stimulation. Animals administered saline exhibited significant increases in TrkA expression and decreases in BACE1 in the stimulated hemisphere relative to the unstimulated. While both nonselective nicotinic and muscarinic acetylcholine receptor blockade attenuated the BACE1 decline, only the nicotinic receptor antagonism blocked the TrkA increase. Next, we applied selective nicotinic antagonists, and the α7 antagonist blocked the TrkA increases, but the α4β2 antagonist did not. BACE1 declines were not blocked by either intervention. Mice with a loxP conditional knockout of the gene for the α7 nicotinic receptor were also employed in these studies. Animals were either stimulated bilaterally for two weeks, or left unstimulated. With or without stimulation, the expression of TrkA receptors was lower in the cortical region with the α7 nicotinic receptor knockdown. We thus conclude that α7 nicotinic receptor activation is necessary for normal expression of TrkA and increases caused by basal forebrain activation, while BACE1 declines caused by stimulation have dependency on a broader array of receptor subtypes.
Analysis of justification for and gender bias in author order among those contributing equally
Authors: Mattoon Ellie Rose , Miles Maisha , Broderick Nichole A , Casadevall Arturo 
Published: March 2024

AbstractThe practice of designating two or more authors as equal contributors (EC) on a scientific publication is increasingly common as a form of sharing credit. However, EC authors are often unclearly attributed on CVs or citation engines, and it is unclear how research teams determine author order within an EC listing. In response to studies showing that male authors were more likely to be placed first in an EC listing, the American Society of Microbiology (ASM) required that authors explain the reasons for author order beginning in 2020. In this study we analyze data from over 2500 ASM publications to see how this policy affected gender bias and how research teams are making decisions on author order. Data on publications from 2018-2021 show that gender bias was largely nonsignificant both before and after authors were asked by ASM to provide an EC statement. The most likely reasons for EC order included alphabetical order, seniority, and chance, although there were differences for publications from different geographic regions. However, many research teams used unique methods in order selection, highlighting the importance of EC statements to provide clarity for readers, funding agencies, and tenure committees.
Creation and manipulation of bipartite expression transgenes inC. elegansusing phiC31 recombinase
Authors: Nonet Michael L. 
Published: March 2024

AbstractBipartite expression systems are widely used in model organisms to express specific gene products in a cell-specific context. They are typically encoded as two independent, unlinked transgenic insertions: a driver and a reporter. Herein, I outline an efficient method namedrecombination-mediated homologexchange (RMHE) that uses genetically encoded phiC31 recombinase to convert driver and reporter transgenes integrated at the same genetic position from atransconfiguration where one component is on each chromosome, to acisconfiguration where the driver and reporter are on the same chromosome. This approach is based upon the development of a set of 3’attBtagged driver lines and 5’attPtagged reporter lines. This genetic based approach leverages both the power of combinatorial re-assortment of drivers and reporters and the simplicity of single locus genetics. I also describe a novel microinjection-based approach namedrecombination-mediated integration (RMI) that utilizes the individualattBdriver andattPreporter lines as landing site for the phiC31 recombinase mediated integration of whole driver and reporter plasmids into the existing reporter and driver lines, respectively. Thus, this work outlines both a novel genetic based and a novel microinjection-based method to create cis-linked driver/reporter pairs. These new tools increase the utility of bipartite systems forC. elegansgenetics by reducing the complexity of reporter system segregation in crosses and thus can greatly simplify the use of bipartite reporter systems during genetic analysis.
Time Cells in the Retrosplenial Cortex
Authors: Subramanian Dev Laxman , Smith David M. 
Published: March 2024

AbstractThe retrosplenial cortex (RSC) is a key component of the brain’s memory systems, with anatomical connections to the hippocampus, anterior thalamus, and entorhinal cortex. This circuit has been implicated in episodic memory and many of these structures have been shown to encode temporal information, which is critical for episodic memory. For example, hippocampal time cells reliably fire during specific segments of time during a delay period. Although RSC lesions are known to disrupt temporal memory, time cells have not been observed there. In the present study, we examined the firing patterns of RSC neurons during the intertrial delay period of two behavioral tasks, a blocked alternation task and a cued T-maze task. For the blocked alternation task, rats were required to approach the east or west arm of a plus maze for reward during different blocks of trials. Because the reward locations were not cued, the rat had to remember the goal location for each trial. In the cued T-maze task, the reward location was explicitly cued with a light and the rats simply had to approach the light for reward, so there was no requirement to hold a memory during the intertrial delay. Time cells were prevalent in the blocked alternation task, and most time cells clearly differentiated the east and west trials. We also found that RSC neurons could exhibit off-response time fields, periods of reliably inhibited firing. Time cells were also observed in the cued T-maze, but they were less prevalent and they did not differentiate left and right trials as well as in the blocked alternation task, suggesting that RSC time cells are sensitive to the memory demands of the task. These results suggest that temporal coding is a prominent feature of RSC firing patterns, consistent with an RSC role in episodic memory.
Synfire Chain Dynamics Unravelling Theta-nested Gamma Oscillations for Balancing Prediction and Dodge in Navigation
Authors: Li Kwan Tung , Wei Yina , Gong Pulin , Yang Dongping 
Published: March 2024

AbstractTheta-nested gamma oscillations, widely observed in experiments, play a crucial role in navigation, yet their functional roles and the origin of the positive correlation between theta frequency and motion velocity remain unclear. We propose that the object’s survival relies on both prediction and dodge – predicting future events and staying alert to unpredictable ones, the latter of which has seldom been considered in goal-navigation tasks. By building a biologically plausible spiking neuronal network model and reproducing experimental results, we leverage synfire chain properties – length and separation – to elucidate the functional roles of theta-nested gamma oscillations: theta oscillations for self-location awareness, gamma oscillations for predictive capabilities and their coupling for enhancing functionality. The positive correlation between theta frequency and motion velocity is demonstrated to optimally balance representing predictable events for planning and staying alert to unexpected events. Our study offers a new avenue for unravelling the neural mechanisms of navigation.
Inferring stability and persistence in the vaginal microbiome: A stochastic model of ecological dynamics
Authors: Ponciano José M. , Gómez Juan P. , Ravel Jacques , Forney Larry J. 
Published: March 2024

AbstractThe interplay of stochastic and ecological processes that govern the establishment and persistence of host-associated microbial communities is not well understood. Here we illustrate the conceptual and practical advantages of fitting stochastic population dynamics models to multi-species bacterial time series data. We show how the stability properties, fluctuation regimes and persistence probabilities of human vaginal microbial communities can be better understood by explicitly accommodating three sources of variability in ecological stochastic models of multi-species abundances: 1) stochastic biotic and abiotic forces, 2) ecological feedback and 3) sampling error. Rooting our modeling tool in stochastic population dynamics modeling theory was key to apply standardized measures of a community’s reaction to environmental variation that ultimately depends on the nature and intensity of the intra-specific and inter-specific interaction strengths. Using estimates of model parameters, we developed a Risk Prediction Monitoring (RPM) tool that estimates temporal changes in persistence probabilities for any bacterial group of interest. This method mirrors approaches that are often used in conservation biology in which a measure of extinction risks is periodically updated with any change in a population or community. Additionally, we show how to use estimates of interaction strengths and persistence probabilities to formulate hypotheses regarding the molecular mechanisms and genetic composition that underpin different types of interactions. Instead of seeking a definition of “dysbiosis” we propose to translate concepts of theoretical ecology and conservation biology methods into practical approaches for the management of human-associated bacterial communities.
Systematics of the fleshy-fruited Sonerileae (Melastomataceae)
Authors: Quakenbush J. Peter , Chen Luo , Penneys Darin S. , Barkman Todd J. , Liu Ying , Yakandawala Deepthi , Veranso-Libalah Marie-Claire , Kadereit Gudrun 
Published: March 2024

ABSTRACTWith approximately 1080 species, Sonerileae is the second largest tribe in the Melastomataceae. Approximately 40% of Sonerileae species belong to fleshy-fruited genera (Catanthera,Heteroblemma,Kendrickia,Medinilla,Pachycentria, andPlethiandra). Relatively few species, especially of the fleshy-fruited taxa, have been sampled for phylogenetic study. Consequently, there is huge uncertainty resulting in many unanswered questions about their evolutionary history, including the monophyly of the largest genus,Medinilla. In this study, the phylogeny of the fleshy-fruited Sonerileae was reconstructed using 385 nuclear and 81 plastid protein-coding loci recovered from target capture. Our study revealed that the fleshy fruited Sonerileae are polyphyletic and belong to three lineages.Kendrickiais sister to an Afrotropical endemic clade.HeteroblemmaandCatantherabelong to a second clade and are most closely related to somePhyllagathisandDriesseniaspecies.Medinillaforms a third clade, and includesPachycentriaandPlethiandra. WithinMedinilla, fifteen clades are identified and characterized. To makeMedinillamonophyletic, the genus is redefined to includePachycentriaandPlethiandra. Major lineages identified withinMedinillalay the groundwork for an infrageneric classification system. Areas of the phylogenetic tree with high conflict or weak sampling are identified to aid further studies in the tribe.
Multiple resistance factors collectively promote inoculum-dependent dynamic survival during antimicrobial peptide exposure inEnterobacter cloacae
Authors: Murtha Andrew N. , Kazi Misha , Kim Eileen , Rosch Kelly M. , Torres Facundo , Dörr Tobias 
Published: March 2024

AbstractAntimicrobial peptides (AMPs) are a promising tool with which to fight rising antibiotic resistance. However, pathogenic bacteria are equipped with several AMP defense mechanisms, whose contributions to AMP resistance are often poorly defined. Here, we evaluate the genetic determinants of resistance to an insect AMP, cecropin B, in the opportunistic pathogenEnterobacter cloacae. Single-cell analysis ofE. cloacae’sresponse to cecropin revealed marked heterogeneity in cell survival, phenotypically reminiscent of heteroresistance (the ability of a subpopulation to grow in the presence of supra-MIC concentration of antimicrobial). The magnitude of this response was highly dependent on initialE. cloacaeinoculum. We identified 3 genetic factors which collectively contribute toE. cloacaeresistance in response to the AMP cecropin: The PhoPQ-two-component system, OmpT-mediated proteolytic cleavage of cecropin, and Rcs-mediated membrane stress response. Altogether, this evidence suggests that multiple, independent mechanisms contribute to AMP resistance inE. cloacae.
Neuronal lysosome transfer to oligodendrocyte precursor cells: a novel mechanism of neuron-glia communication and its role in neurodegenerative diseases
Authors: Fang Li-Pao , Lin Ching-Hsin , Medlej Yasser , Zhao Renping , Chang Hsin-Fang , Su Yixun , Zhao Na , Gobbo Davide , Guo Qilin , Wyatt Amanda , Wahl Vanessa , Boehm Ulrich , Huang Wenhui , Lauterbach Marcel A. , Yi Chenju , Niu Jianqin , Scheller Anja , Kirchhoff Frank , Bai Xianshu 
Published: March 2024

AbstractOligodendrocyte precursor cells (OPCs) shape brain function through intricate regulatory mechanisms. Here, we observed that OPC processes establish connections with neuronal somata, with smaller lysosomes positioned near these contact sites. Tracking lysosomes demonstrated neuronal lysosomes were attracted to and released at these contact points, eventually becoming incorporated into OPC processes, suggesting a selective, OPC-evoked release of lysosomes from neuronal soma and their ingestion by OPCs, highlighting a unique lysosome-mediated communication between neurons and OPCs. Diminished branching of OPC processes resulted in fewer neuron-OPC contacts, fostering larger lysosome accumulation in neurons, altered neuronal activity and escalated prevalence of senescent neurons during aging. A similar reduction in OPC branching and neuronal lysosome accumulation was evident in an early-stage Alzheimer’s disease mouse model. Together, these findings underscore the pivotal role of OPC processes in modulating neuronal activity through direct somatic contact and lysosome ingestion, presenting a prospective therapeutic avenue for addressing neurodegenerative diseases.
Developing Bioactive Hydrogels Containing Cell-derived Extracellular Matrix: Implications in Drug and Cell-free Bone and Cartilage Repair
Authors: Coyle Ali , Chakraborty Aishik , Huang Jiaqi , Shamiya Yasmeen , Luo Wei , Paul Arghya 
Published: March 2024

AbstractThe prevalence of osteoarthritis has been increasing in aging populations, which has necessitated the use of advanced biomedical treatments. These involve grafts or delivering drug molecules entrapped in scaffolds. However, such treatments often show suboptimal therapeutic effects due to poor half-life and off-target effects of drug molecules. This study aims to overcome these limitations by 3D printing gelatin-based hydrogel scaffolds containing cell-derived extracellular matrix (ECM) as the bioactive therapeutic cargo. Here, pre-osteoblastic and pre-chondrogenic murine cells were differentiatedin vitro, decellularized, and incorporated into methacrylated gelatin (GelMA) solutions to form osteogenic (GelO) and chondrogenic (GelC) hydrogels, respectively. The integration of the bioactive decellularized extracellular matrix (dECM) allows GelO and GelC to induce differentiation in human adipose-derived stem cells (hADSCs) toward osteogenic and chondrogenic lineages. GelO and GelC can be covalently adhered using carbodiimide coupling reaction, forming bioactive osteochondral plug. Moreover, this osteochondral plug can also induce differentiation of hADSCs. To conclude, this ECM-based bioactive hydrogel offers a promising new drug-free and cell-free treatment strategy for bone and cartilage repair, and future osteoarthritis management.