bluuebunny/crossref_metadata_2025_split huggingface dataset:
A deep dive into theFALSIFLORAcontribution to tomato reproductive development through a comprehensive allelic series analysis
Authors: Quevedo-Colmena Abraham S. , Vriezen Wim H. , Wesselink Pieter G.A. , Pérez José M. , Pineda Benito , García-Sogo Begoña , Angosto Trinidad , Moreno Vicente , Yuste-Lisbona Fernando J. , Lozano Rafael 
Published: May 2024

AbstractPlants undergo continuous growth and development thanks to meristems, specialized groups of pluripotent stem cells that remain in their undifferentiated state throughout the plant’s life cycle. Meristem transition from the vegetative to the reproductive phase heavily influences plant reproductive success and agricultural productivity. In tomato (Solanum lycopersicumL.),FALSIFLORA(FA), the orthologue of the ArabidopsisLEAFYgene, promotes floral transition by specifying floral meristem identity and regulating the expression of genes responsible for floral organ identity and development. In this study, the allelic series ofFAhas been expanded by combining the screening of a tomato EMS mutant collection with overexpression, gene silencing and CRISPR/Cas9 genome editing approaches, aimed to deepen the understanding of the functional role ofFAduring tomato reproductive development. The phenotypic and molecular characterization of theFAallelic series revealed the multifaceted role ofFAacting in both early and late stages of floral ontogeny. Thus, in addition to promoting floral transition and specifying floral meristem identity,FAalso plays a role in inflorescence meristem maturation and termination, thereby regulating the inflorescence architecture. Furthermore,FAexerts regulatory control over the expression of the tomato homologs ofAGAMOUS(TOMATO AGAMOUS1,TAG1) andWUSCHEL(SlWUS), underscoring its function in promoting carpel development and suppressing floral stem cell activity, thereby establishing floral determinacy. In conclusion, our findings demonstrate the potential of employing mutant allelic series as powerful tools for elucidating gene functions and deciphering the intricate molecular basis underlying biological processes.Plain Language SummaryOur research aims to gain a deeper understanding of the role ofFALSIFLORAin tomato reproductive development. TheFALSIFLORAallelic spectrum was expanded through mutant screening, along with overexpression, silencing, and CRISPR/Cas9 editing approaches. Our findings reveal thatFALSIFLORAhas a dual function in early and late floral development stages. In addition to promoting floral transition and specifying floral meristem identity,FAregulates the expression of tomato genes homologous toWUSCHELandAGAMOUS, which play an essential role in stem cell regulation and carpel development. This study highlights the value of allelic series in elucidating gene functions and intricate biological mechanisms.
Activity of prefrontal cortex serotonin 2A receptor expressing neurons is necessary for the head-twitch response of mice to psychedelic drug DOI in a sex-dependent manner
Authors: Ozols Annika B. , Wei Jing , Campbell Janet M. , Hu Chengcheng , Qiu Shenfeng , Gallitano Amelia L. 
Published: May 2024

AbstractSerotonin 2A receptors (5-HT2ARs) mediate the effects of psychedelic drugs. 5-HT2AR agonists, such as (-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI), that produce a psychedelic experience in humans induce a head-twitch response (HTR) behavior in rodents. However, it is unknown whether the activity of 5-HT2AR expressing neurons is sufficient to produce the HTR in the absence of an agonist, or in which brain region 5-HT2ARs control the HTR. Here, we use an optogenetic approach to examine whether activation of 5-HT2AR expressing neurons in the mouse prefrontal cortex (PFC) is sufficient to induce HTRs alone, or may augment the HTR produced by DOI, and if inhibition of these neurons prevents DOI-induced HTRs in mice. We crossedHtr2a-Cre mice to Cre-dependent optogenetic lines Ai32 (channelrhodopsin) and Ai39 (halorhodopsin) to selectively activate and inhibit (respectively) 5-HT2AR-expressing neurons in the PFC of adult mice. We found that optogenetic stimulation of PFC 5-HT2AR expressing neurons in the absence of an agonist does not increase HTRs in mice. In both male and female Ai32 mice that received vehicle, there was no difference in HTRs in mice that expressedHtr2a-Cre compared with control mice, indicating that optogenetic activation of 5-HT2AR+ cells in the PFC was not sufficient to produce HTRs in the absence of an agonist. In female mice, activation of PFC 5-HT2AR expressing neurons augmented the HTR produced by DOI. However, this result was not seen inmalemice. In contrast, inhibition of 5-HT2AR expressing neurons in the PFC prevented the increase in HTR produced by DOI in male, but not in female, mice. Together, these findings suggest that activation of 5-HT2ARs in the PFC is not sufficient to induce HTRs in the absence of a 5-HT2AR agonist but is necessary for induction of HTRs by a 5-HT2AR agonist in a sex-dependent manner.
MicroRNA-374b regulates SARS-CoV-2 viral protein mediated endothelial to mesenchymal transition by targeting c-FLIP
Authors: Raji Grace R. , Poyyakkara Aswini , Ramachandran Vishnu , Anjali K , Sameer Kumar VB 
Published: May 2024

AbstractThe pathophysiological consequences of COVID-19 disease are still unclear, however, endothelial cell (EC) dysfunction has been observed to play a key role in disease progression and severity. Many reports suggests that SARS-CoV-2 mediated endothelial dysfunction is the result of intracellular signaling initiated by the binding of the spike protein to ACE2, which can modify endothelial cell phenotype. Recent reports suggests endothelial to mesenchymal transition (Endo MT) as a process heavily involved in lung fibrosis of COVID 19 patients. EndoMT is involved in many chronic and fibrotic diseases and appears to be regulated by complex molecular mechanisms and different signaling pathways, in particular microRNAs (miRNAs), which constitute a crucial mediator of EndoMT. MicroRNAs (miRNAs), small endogenous RNA molecules that regulate several physiological processes including endothelial homeostasis, and vascular diseases, can be perturbed by infecting viruses. Based on these facts, this study was designed to decipher the role of miR-374b, which was found to be significantly downregulated upon profiling of SARS-CoV-2 viral protein stimulated endothelial cells. Gene profiling of endothelial cells revealed c-FLIP (CFLAR) to be among the most significantly upregulated gene. In silico target prediction analysis using targetscan revealed c-FLIP as the major target of miR-374b. Further it was identified that miR-374b can reverse c-FLIP mRNA and protein levels in SARS-CoV-2 viral protein stimulated endothelial cells under conditions of miR-374b overexpression. Since vascular dysfunction involve, under many circumstances, loss of vascular tone due to mesenchymal transition of endothelial cells, we next checked if fibrotic events are initiated downstream of c-FLIP pathway. Further mechanistic studies involving identification of the expression pattern of mesenchymal markers in SARS-CoV-2 viral protein stimulated endothelial cells in presence or absence of miR-374b provide evidence for the important role of miR-374b in regulating SARS CoV-2 mediated EndoMT and fibrotic events downstream of c-FLIP pathway and may highlight possible new therapeutic approaches targeted at the damaged endothelium.
Fast and robust objective EEG audiometry
Authors: Guyonnet-Hencke T. , Portoles O. , de Vries M. , Koderman E. , Winkler A. , Goodall J. , Desain P. , Thielen J. , Schulte M. , Beynon A. J. , van Kesteren M. 
Published: May 2024

AbstractThe current ‘gold standard’ of audiometry relies on subjective behavioral responses, which is impractical and unreliable for certain groups such as children, individuals with severe disabilities, or the disabled elderly. This study presents a novel electroencephalography (EEG) system that is easy to setup and estimates audiometric thresholds quickly. Air-conduction audiometric thresholds at 250, 500, 1000, 2000, 4000, and 8000 Hz and 5 dB resolution were estimated from ten elderly patients with asymmetric sensorineural hearing loss and five normal hearing young adults using three different systems: the novel EEG system, conventional pure-tone audiometry (PTA), and an automated behavioral test with the same stimulus properties as in the EEG test. EEG data was collected for 15 minutes from 32 semi-dry EEG electrodes. Later, the EEG system was trimmed to 8 electrodes and 7.5 minutes of data with satisfactory results. Correlation and regression analysis validated the hearing thresholds derived from both EEG configurations relative to the behavioral hearing thresholds–Pearson’s correlation of 0.82 between PTA and 8-electrode 7.5-minute EEG data. The results of this study open the door to fast and objective hearing threshold estimation with EEG.
Mechanisms of axoneme and centriole elimination inNaegleria gruberi
Authors: Woglar Alexander , Busso Coralie , Garcia-Rodriguez Gabriela , Douma Friso , Croisier-Coeytaux Mary-Claude , Knott Graham , Gönczy Piere 
Published: May 2024

AbstractThe excavateNaegleria gruberi,a basal eukaryote related to the “brain eating”Naegleria fowleri, can transform transiently from an amoeboid life form lacking flagella and centrioles to a flagellate life form where these elements are present, followed by reversion to an amoeboid state. The mechanisms imparting elimination of axonemes and centrioles during this reversion process are not known. Here, we uncover that flagella primarily fold onto the cell surface and fuse within milliseconds with the plasma membrane. Once internalized, axonemes are severed by Spastin into equally-sized fragments, which are then enclosed by membranes, after which their contents are eliminated through the lysosomal pathway. Moreover, we discovered that centrioles undergo progressive K63 autophagy-linked poly-ubiquitination and K48 proteasome-promoting poly-ubiquitination, and that ubiquitination occurs next to centriolar microtubules. Most centrioles are eliminated in lysosomes or the cytoplasm in a lysosomal- and proteasome-dependent manner. Strikingly, we uncover in addition that centrioles can be shed in the extracellular milieu and taken up by other cells. Collectively, these findings reveal fundamental mechanisms governing the elimination of essential cellular constituents inNaegleriathat may operate broadly in eukaryotic systems.IMPORTANTManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way.Upon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor.The identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report.The identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred.GUIDELINESFor reviewers:https://www.reviewcommons.org/reviewersFor authors:https://www.reviewcommons.org/authorsCONTACTThe Review Commons office can be contacted directly at:office@reviewcommons.org
Biological activity of a stable 6-aryl-2-benzoyl-pyridine colchicine-binding site inhibitor, 60c, in metastatic, triple-negative breast cancer
Authors: Oluwalana Damilola , Adeleye Kelli L , Krutilina Raisa I , Chen Hao , Playa Hilaire , Deng Shanshan , Parke Deanna N , Abernathy John , Middleton Leona , Cullom Alexandra , Thalluri Bhargavi , Ma Dejian , Meibohm Bernd , Miller Duane D , Seagroves Tiffany N , Li Wei 
Published: May 2024

AbstractBackgroundImproving survival for patients diagnosed with metastatic disease and overcoming chemoresistance remain significant clinical challenges in treating breast cancer. Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by a lack of therapeutically targetable receptors (ER/PR/HER2). TNBC therapy includes a combination of cytotoxic chemotherapies, including microtubule-targeting agents (MTAs) like paclitaxel (taxane class) or eribulin (vinca class); however, there are currently no FDA-approved MTAs that bind to the colchicine-binding site. Approximately 70% of patients who initially respond to paclitaxel will develop taxane resistance (TxR). We previously reported that an orally bioavailable colchicine-binding site inhibitor (CBSI), VERU-111, inhibits TNBC tumor growth and treats pre-established metastatic disease. To further improve the potency and metabolic stability of VERU-111, we created next-generation derivatives of its scaffold, including 60c.Results60c shows improved in vitro potency compared to VERU-111 for taxane-sensitive and TxR TNBC models, and suppress TxR primary tumor growth without gross toxicity. 60c also suppressed the expansion of axillary lymph node metastases existing prior to treatment. Comparative analysis of excised organs for metastasis between 60c and VERU-111 suggested that 60c has unique anti-metastatic tropism. 60c completely suppressed metastases to the spleen and was more potent to reduce metastatic burden in the leg bones and kidney. In contrast, VERU-111 preferentially inhibited liver metastases and lung metastasis repression was similar. Together, these results position 60c as an additional promising CBSI for TNBC therapy, particularly for patients with TxR disease.
Structural Determinants ofVibrio choleraeFeoB Nucleotide Promiscuity
Authors: Lee Mark , Magante Kate , Gómez-Garzón Camilo , Payne Shelley M. , Smith Aaron T. 
Published: May 2024

ABSTRACTFerrous iron (Fe2+) is required for the growth and virulence of many pathogenic bacteria, includingVibrio cholerae(Vc), the causative agent of the disease cholera. For this bacterium, Feo is the primary system that transports Fe2+into the cytosol. FeoB, the main component of this system, is regulated by a soluble cytosolic domain termed NFeoB. Recent reanalysis has shown that NFeoBs can be classified as either GTP-specific or NTP-promiscuous, but the structural and mechanistic bases for these differences were not known. To explore this intriguing property of FeoB, we solved the X-ray crystal structures ofVcNFeoB in both the apo and GDP-bound forms. Surprisingly, this promiscuous NTPase displayed a canonical NFeoB G-protein fold like GTP-specific NFeoBs. Using structural bioinformatics, we hypothesized that residues surrounding the nucleobase could be important for both nucleotide affinity and specificity. We then solved the X-ray crystal structures of N150TVcNFeoB in the apo and GDP-bound forms to reveal H-bonding differences surround the guanine nucleobase. Interestingly, isothermal titration calorimetry revealed similar binding thermodynamics of the WT and N150T proteins to guanine nucleotides, while the behavior in the presence of adenine nucleotides was dramatically different. AlphaFold models ofVcNFeoB in the presence of ADP and ATP showed important conformational changes that contribute to nucleotide specificity among FeoBs. Combined, these results provide a structural framework for understanding FeoB nucleotide promiscuity, which could be an adaptive measure utilized by pathogens to ensure adequate levels of intracellular iron across multiple metabolic landscapes.
Anchorage of H3K9-methylated heterochromatin to the nuclear periphery helps mediate P-cell nuclear migration though constricted spaces inCaenorhabditis elegans
Authors: Gregory Ellen F. , Luxton G.W. Gant , Starr Daniel A. 
Published: May 2024

ABSTRACTNuclei adjust their deformability while migrating through constrictions to enable structural changes and maintain nuclear integrity. The effect of heterochromatin anchored at the nucleoplasmic face of the inner nuclear membrane on nuclear morphology and deformability duringin vivonuclear migration through constricted spaces remains unclear. Here, we show that abolishing peripheral heterochromatin anchorage by eliminating CEC-4, a chromodomain protein that tethers H3K9-methylated chromatin to the nuclear periphery, disrupts constrained P-cell nuclear migration inCaenorhabditis eleganslarvae in the absence of the established LINC complex-dependent pathway. CEC-4 acts in parallel to an actin and CDC-42-based pathway. We also demonstrate the necessity for the chromatin methyltransferases MET-2 and JMJD-1.2 during P-cell nuclear migration in the absence of functional LINC complexes. We conclude that H3K9-nethylated chromatin needs to be anchored to the nucleoplasmic face of the inner nuclear membrane to help facilitate nuclear migration through constricted spacesin vivo.
Lipidomics and colistin resistance in non-human isolates ofAcinetobacter seifertii
Authors: Sykes Ellen M. E. , Mateo-Estrada Valeria , Muzaleva Anna , Zhanel George , Dettman Jeremy , Chapados Julie , Gerdis Suzanne , Khan Izhar U. H. , Castillo-Ramírez Santiago , Kumar Ayush 
Published: May 2024

AbstractAcinetobacter baumanniiis most well known for its role as a human pathogen and as a member of theAcinetobacter calcoaceticus-baumannii(ACB) complex. However, lesser characterised members of the ACB complex, have also been implicated in hospital-acquired infections. Once mainly considered opportunistic pathogens, manyA. baumanniiand non-baumanniistrains are being isolated from agricultural, water and food sources. The surveillance and tracking ofAcinetobacterspp. have been recently suggested to be part of the One Health consortium, to understand and prevent the spread of antimicrobial resistance. Here, we isolated fourAcinetobacterstrains from tank milk in Bogor, Indonesia and using ANI and dDDH techniques have identified them asAcinetobacter seifertii. MLST methods assigned theseA. seifertiistrains to a novel Sequence Types (ST), highlighting the diversity not only within the ACB complex but also in non-humanAcinetobacterspp. These fourA. seifertiistrains are colistin-resistant and while they do not harbour any known mechanism of colistin resistance, they do share amino acid substitutions in regulatory proteins, AdeS, PmrAB, H-NS, and the membrane associated proteins, LpxACD, MlaD, PldA, LpsB and EptA that may contribute to this phenotype. Furthermore, down-regulation of the RND efflux pump AdeAB, may also be a key factor in colistin resistance in these non-humanA. seifertiistrains. Lipidomics revealed an acyl-homoserine lactone (AHL) molecule, and lyso-phosphatidylethanolamine (lyso-PE) in significant abundance compared to colistin-sensitiveA. baumanniiATCC17978 revealing lipidomic differences between species. Finally, these four tank milkA. seifertiistrains are avirulent in an insect model of virulence. It is possible thatA. seifertiistrains are intrinsically resistant to colistin and require further study. By investigating these less understoodAcinetobacterspp. from non-human sources, our study supports the One Health approach to combatting antibiotic resistance.
Lattice investigations of the chimera baryon spectrum in the
Sp(4)
gauge theory
Authors: Bennett Ed , Hong Deog Ki , Hsiao Ho , Lee Jong-Wan , Lin C.-J. David , Lucini Biagio , Piai Maurizio , Vadacchino Davide 
Published: May 2024

We report the results of lattice numerical studies of the Sp(4) gauge theory coupled to fermions (hyperquarks) transforming in the fundamental and two-index antisymmetric representations of the gauge group. This strongly coupled theory is the minimal candidate for the ultraviolet completion of composite Higgs models that facilitate the mechanism of partial compositeness for generating the top-quark mass. We measure the spectrum of the low-lying, half-integer spin, bound states composed of two fundamental and one antisymmetric hyperquarks, dubbed chimera baryons, in the quenched approximation. In this first systematic, nonperturbative study, we focus on the three lightest parity-even chimera-baryon states, in analogy with QCD, denoted as ΛCB, ΣCB (both with spin 1/2), and ΣCB* (with spin 3/2). The spin-1/2 such states are candidates of the top partners. The extrapolation of our results to the continuum and massless-hyperquark limit is performed using formulas inspired by QCD heavy-baryon Wilson chiral perturbation theory. Within the range of hyperquark masses in our simulations, we find that ΣCB is not heavier than ΛCB.

Published by the American Physical Society
2024
Design and validation of the evolved version of the tactical separation system
Authors: Di Vito Vittorio , Torrano Giulia , Cerasuolo Giovanni , Ferrucci Michele 
Published: May 2024

Purpose
The small air transport (SAT) domain is gaining increasing interest over the past decade, based on its perspective relevance in enabling efficient travel over a regional range, by exploiting small airports and fixed wing aircraft with up to 19 seats (EASA CS-23 category). To support its wider adoption, it is needed to enable single pilot operations.

Design/methodology/approach
An integrated mission management system (IMMS) has been designed and implemented, able to automatically optimize the aircraft path by considering trajectory optimization needs. It takes into account both traffic scenario and weather actual and forecasted condition and is also able to select best destination airport, should pilot incapacitation occur during flight. As part of the IMMS, dedicated evolved tactical separation system (Evo-TSS) has been designed to provide elaboration of both surrounding and far located traffic and subsequent traffic clustering, to support the trajectory planning/re-planning by the IMMS.

Findings
The Clean Sky 2-funded project COAST (Cost Optimized Avionics SysTem) successfully designed and validated through flight demonstrations relevant technologies enabling affordable cockpit and avionics and supporting single pilot operations for SAT vehicles. These technologies include the TSS in its baseline and evolved versions, included in the IMMS.

Originality/value
This paper describes the TSS baseline version and the basic aspects of the Evo-TSS design. It is aimed to outline the implementation of the Evo-TSS dedicated software in Matlab/Simulink environment, the planned laboratory validation campaign and the results of the validation exercises in fast-time Matlab/Simulink environment, which were successfully concluded in 2023.
Wholesale price forecasts of green grams using the neural network
Authors: Jin Bingzi , Xu Xiaojie 
Published: May 2024

PurposeAgriculture commodity price forecasts have long been important for a variety of market players. The study we conducted aims to address this difficulty by examining the weekly wholesale price index of green grams in the Chinese market. The index covers a ten-year period, from January 1, 2010, to January 3, 2020, and has significant economic implications.Design/methodology/approachIn order to address the nonlinear patterns present in the price time series, we investigate the nonlinear auto-regressive neural network as the forecast model. This modeling technique is able to combine a variety of basic nonlinear functions to approximate more complex nonlinear characteristics. Specifically, we examine prediction performance that corresponds to several configurations across data splitting ratios, hidden neuron and delay counts, and model estimation approaches.FindingsOur model turns out to be rather simple and yields forecasts with good stability and accuracy. Relative root mean square errors throughout training, validation and testing are specifically 4.34, 4.71 and 3.98%, respectively. The results of benchmark research show that the neural network produces statistically considerably better performance when compared to other machine learning models and classic time-series econometric methods.Originality/valueUtilizing our findings as independent technical price forecasts would be one use. Alternatively, policy research and fresh insights into price patterns might be achieved by combining them with other (basic) prediction outputs.