bluuebunny/crossref_metadata_2025_split huggingface dataset:
The dynamics of colicin E9 release from Escherichia coli in native conditions
Authors: Bano Shaista , Tunio Sarfraz Ali , Penfold Christopher N , James Richard 
Published: April 2024

Abstract
Colicin (Col) plasmid contains colicin encoding genes arranged in an operon controlled by an SOS inducible promoter. Therefore, any external stresses to the host cell can induce the expression of the downstream genes in the Col operon, including a lysis gene. The lysis protein is involved in the extracellular release of colicin through lysis of the producer cells, which causes a decline in culture turbidity. However, it is not yet known that E. coli cells with the native pColE9-J plasmid hold the same level of cell death at the population level following a set of induced conditions. In this study, using a mitomycin C sensitivity assay along with a live dead staining method of detection, we showed that the native pColE9-J plasmid, which unusually carries an extended Col operon (ColE9) containing two lysis genes, did not confer a rapid decline in the culture turbidity following induction with mitomycin C. Interestingly a subset of the cells suffered perturbation of their outer membrane, which was not observed from single lysis mutant (∆celE or ∆celI) cells. This observed heterogeneity in the colicin E9 release leading to differential outer membrane perforation may bring a competitive advantage to these cells in a mixed population.
Epidemiology and management of tinea capitis in France: A 6-year nationwide retrospective survey
Authors: Gangneux Jean-Pierre , Miossec Charline , Machouart Marie , Gits-Muselli Maud , Benderdouche Mazouz , Ranque Stéphane , Botterel Françoise , Brun Sophie ,   for the SFMM Tinea capitis study group, Damiani Céline , Pihet Marc , Benderdouce Mazouz , Botterel Françoise , Brun Sophie , Fekkar Arnaud , Foulet Françoise , Gits-Muselli Maud , Hamane Samia , Moreno-Sabater Alicia , Sitterlé Emilie , Bellanger Anne-Pauline , Gabriel Frédéric , Quinio Dorothée , Nourrisson Céline , Sautour Marc , Cognet Odile , Pelloux Hervé , Nicolas Muriel , Bouteille Bernard , Durieux Marie-Fleur , Deleplancque Anne-Sophie , Persat Florence , Ranque Stéphane , Miossec Charline , Desbois Nicole , Schneider Christine , Machouart Marie , Debourgogne Anne , Lavergne Rose-Anne , Hasseine Lilia , Cremer Geneviève , Cateau Estelle , Huguenin Antoine , Gangneux Jean-Pierre , Guegan Hélène , Belaz Sorya , Lepoutre Xavier , Favennec Loïc , Letscher-Bru Valérie , Camin-Ravenne Anne-Marie , Cassaing Sophie , Desoubeaux Guilllaume , Moreau Farida 
Published: April 2024

Abstract
Tinea capitis (TC) is still a frequent dermatophytosis in France, both autochthonous and imported. A nationwide retrospective survey was performed and a total of 4395 TC cases were recorded within 36 French mycology laboratories during a 6-year period. TC is a disease that occurs in childhood with 85% of the cases occurring before 10 years old and 94% before the age of 15. Anthropophilic origin was predominant with 779 cases of Trichophyton tonsurans (32.6%), 738 cases of Trichophyton soudanense/T. violaceum (31%), and 445 cases of Microsporum audouinii (19.2%). Of note, T. tonsurans represents more than 80% of the cases in the French West Indies (Martinique and Guadeloupe). By contrast, zoophilic species were less prevalent with mainly M. canis (10.3%) confirming the shift from zoophilic to anthropophilic species observed in many centers during the last decades. During this survey, diagnosis methods were also collected. Most labs had a classical process for the diagnosis: microscopic direct examination associated to cultures on Sabouraud and Sabouraud-cycloheximide media (incubated between 25 ± 5°C for at least 3 weeks) in all laboratories. Identification of the causal dermatophyte was performed by microscopic and macroscopic examination of the cultures in 100% of the labs, with various specific culture media available when fructification was insufficient (mainly malt or potato-dextrose agar, or Borelli medium). New techniques were also implemented with the introduction of MALDI-TOF mass spectrometry identification in more than two third of the labs, and molecular identification available if necessary in half of the labs.
Mitigating bias in deep learning: training unbiased models on biased data for the morphological classification of galaxies
Authors: Medina-Rosales Esteban , Cabrera-Vives Guillermo , Miller Christopher J 
Published: April 2024

ABSTRACT
Galaxy morphologies and their relation with physical properties have been a relevant subject of study in the past. Most galaxy morphology catalogues have been labelled by human annotators or by machine learning models trained on human-labelled data. Human-generated labels have been shown to contain biases in terms of the observational properties of the data, such as image resolution. These biases are independent of the annotators, that is, are present even in catalogues labelled by experts. In this work, we demonstrate that training deep learning models on biased galaxy data produces biased models, meaning that the biases in the training data are transferred to the predictions of the new models. We also propose a method to train deep learning models that considers this inherent labelling bias, to obtain a de-biased model even when training on biased data. We show that models trained using our deep de-biasing method are capable of reducing the bias of human-labelled data sets.
smarty: The MILES moderate resolution near-infrared stellar library
Authors: Bertoldo-Coêlho Michele , Riffel Rogério , Trevisan Marina , Dametto Natacha Zanon , Dahmer-Hahn Luis , Coelho Paula , Martins Lucimara , Ruschel-Dutra Daniel , Vazdekis Alexandre , Rodríguez-Ardila Alberto , Chies-Santos Ana L , Riffel Rogemar A , La Barbera Francesco , Martín-Navarro Ignacio , Falcón-Barroso Jesus , Moura Tatiana 
Published: April 2024

ABSTRACT
Most of the observed galaxies cannot be resolved into individual stars and are studied through their integrated spectrum using simple stellar populations (SSPs) models, with stellar libraries being a key ingredient in building them. Spectroscopic observations are increasingly being directed towards the near-infrared (NIR), where much is yet to be explored. SSPs in the NIR are still limited, and there are inconsistencies between different sets of models. One of the ways to minimize this problem is to have reliable NIR stellar libraries. The main goal of this work is to present smarty (mileS Moderate resolution neAr-infRared sTellar librarY) a ∼0.9−2.4 $\mu$m stellar spectral library composed of 31 stars observed with the Gemini Near-IR Spectrograph (GNIRS) at the 8.1 m Gemini North telescope and make it available to the community. The stars were chosen from the miles library, for which the atmospheric parameters are reliable (and well-tested), to populate different regions of the Hertzsprung–Russell (HR) diagram. Furthermore, five of these stars have NIR spectra available that we use to assess the quality of smarty. The remaining 26 stars are presented for the first time in the NIR. We compared the observed smarty spectra with synthetic and interpolated spectra, finding a mean difference of $\sim 20~{{\ \rm per\ cent}}$ in the equivalent widths and ∼1 per cent in the overall continuum shape in both sets of comparisons. We computed the spectrophotometric broad-band magnitudes and colours and compared them with the 2MASS ones, resulting in mean differences up to 0.07 and 0.10 mag in magnitudes and colours, respectively. In general, a small difference was noted between the smarty spectra corrected using the continuum from the interpolated and the theoretical stars.
MAUVE: a 6 kpc bipolar outflow launched from NGC 4383, one of the most H i-rich galaxies in the Virgo cluster
Authors: Watts Adam B , Cortese Luca , Catinella Barbara , Fraser-McKelvie Amelia , Emsellem Eric , Coccato Lodovico , van de Sande Jesse , Brown Toby H , Ascasibar Yago , Battisti Andrew , Boselli Alessandro , Davis Timothy A , Groves Brent , Thater Sabine 
Published: April 2024

ABSTRACT
Stellar feedback-driven outflows are important regulators of the gas–star formation cycle. However, resolving outflow physics requires high-resolution observations that can only be achieved in very nearby galaxies, making suitable targets rare. We present the first results from the new VLT/MUSE large programme MAUVE (MUSE and ALMA Unveiling the Virgo Environment), which aims to understand the gas–star formation cycle within the context of the Virgo cluster environment. Outflows are a key part of this cycle, and we focus on the peculiar galaxy NGC 4383, which hosts a $\sim\!\! 6\,$ kpc bipolar outflow fuelled by one of Virgo’s most H i-rich discs. The spectacular MUSE data reveal the clumpy structure and complex kinematics of the ionized gas in this M82-like outflow at 100 pc resolution. Using the ionized gas geometry and kinematics, we constrain the opening half-angle to θ = 25–35°, while the average outflow velocity is $\sim\!\! 210\ \text{km} \, \text{s}^{-1}$. The emission line ratios reveal an ionization structure where photoionization is the dominant excitation process. The outflowing gas shows a marginally elevated gas-phase oxygen abundance compared to the disc but lower than the central starburst, highlighting the contribution of mixing between the ejected and entrained gas. Making some assumptions about the outflow geometry, we estimate an integrated mass outflow rate of $\sim\!\! 1.8~\mathrm{M}_{\odot } \, \mathrm{yr}^{-1}$ and a corresponding mass-loading factor in the range of 1.7–2.3. NGC 4383 is a useful addition to the few nearby examples of well-resolved outflows, and will provide a useful baseline for quantifying the role of outflows within the Virgo cluster.
Extensive long-range polycomb interactions and weak compartmentalization are hallmarks of human neuronal 3D genome
Authors: Pletenev Ilya A , Bazarevich Maria , Zagirova Diana R , Kononkova Anna D , Cherkasov Alexander V , Efimova Olga I , Tiukacheva Eugenia A , Morozov Kirill V , Ulianov Kirill A , Komkov Dmitriy , Tvorogova Anna V , Golimbet Vera E , Kondratyev Nikolay V , Razin Sergey V , Khaitovich Philipp , Ulianov Sergey V , Khrameeva Ekaterina E 
Published: April 2024

AbstractChromatin architecture regulates gene expression and shapes cellular identity, particularly in neuronal cells. Specifically, polycomb group (PcG) proteins enable establishment and maintenance of neuronal cell type by reorganizing chromatin into repressive domains that limit the expression of fate-determining genes and sustain distinct gene expression patterns in neurons. Here, we map the 3D genome architecture in neuronal and non-neuronal cells isolated from the Wernicke's area of four human brains and comprehensively analyze neuron-specific aspects of chromatin organization. We find that genome segregation into active and inactive compartments is greatly reduced in neurons compared to other brain cells. Furthermore, neuronal Hi-C maps reveal strong long-range interactions, forming a specific network of PcG-mediated contacts in neurons that is nearly absent in other brain cells. These interacting loci contain developmental transcription factors with repressed expression in neurons and other mature brain cells. But only in neurons, they are rich in bivalent promoters occupied by H3K4me3 histone modification together with H3K27me3, which points to a possible functional role of PcG contacts in neurons. Importantly, other layers of chromatin organization also exhibit a distinct structure in neurons, characterized by an increase in short-range interactions and a decrease in long-range ones.
Live-cell imaging reveals the trade-off between target search flexibility and efficiency for Cas9 and Cas12a
Authors: Olivi Lorenzo , Bagchus Cleo , Pool Victor , Bekkering Ezra , Speckner Konstantin , Offerhaus Hidde , Wu Wen Y , Depken Martin , Martens Koen J A , Staals Raymond H J , Hohlbein Johannes 
Published: April 2024

Abstract
CRISPR-Cas systems have widely been adopted as genome editing tools, with two frequently employed Cas nucleases being SpyCas9 and LbCas12a. Although both nucleases use RNA guides to find and cleave target DNA sites, the two enzymes differ in terms of protospacer-adjacent motif (PAM) requirements, guide architecture and cleavage mechanism. In the last years, rational engineering led to the creation of PAM-relaxed variants SpRYCas9 and impLbCas12a to broaden the targetable DNA space. By employing their catalytically inactive variants (dCas9/dCas12a), we quantified how the protein-specific characteristics impact the target search process. To allow quantification, we fused these nucleases to the photoactivatable fluorescent protein PAmCherry2.1 and performed single-particle tracking in cells of Escherichia coli. From our tracking analysis, we derived kinetic parameters for each nuclease with a non-targeting RNA guide, strongly suggesting that interrogation of DNA by LbdCas12a variants proceeds faster than that of SpydCas9. In the presence of a targeting RNA guide, both simulations and imaging of cells confirmed that LbdCas12a variants are faster and more efficient in finding a specific target site. Our work demonstrates the trade-off of relaxing PAM requirements in SpydCas9 and LbdCas12a using a powerful framework, which can be applied to other nucleases to quantify their DNA target search.
Comprehensive genomic features indicative for Notch responsiveness
Authors: Giaimo Benedetto Daniele , Friedrich Tobias , Ferrante Francesca , Bartkuhn Marek , Borggrefe Tilman 
Published: April 2024

Abstract
Transcription factor RBPJ is the central component in Notch signal transduction and directly forms a coactivator complex together with the Notch intracellular domain (NICD). While RBPJ protein levels remain constant in most tissues, dynamic expression of Notch target genes varies depending on the given cell-type and the Notch activity state. To elucidate dynamic RBPJ binding genome-wide, we investigated RBPJ occupancy by ChIP-Seq. Surprisingly, only a small set of the total RBPJ sites show a dynamic binding behavior in response to Notch signaling. Compared to static RBPJ sites, dynamic sites differ in regard to their chromatin state, binding strength and enhancer positioning. Dynamic RBPJ sites are predominantly located distal to transcriptional start sites (TSSs), while most static sites are found in promoter-proximal regions. Importantly, gene responsiveness is preferentially associated with dynamic RBPJ binding sites and this static and dynamic binding behavior is repeatedly observed across different cell types and species. Based on the above findings we used a machine-learning algorithm to predict Notch responsiveness with high confidence in different cellular contexts. Our results strongly support the notion that the combination of binding strength and enhancer positioning are indicative of Notch responsiveness.
admetSAR3.0: a comprehensive platform for exploration, prediction and optimization of chemical ADMET properties
Authors: Gu Yaxin , Yu Zhuohang , Wang Yimeng , Chen Long , Lou Chaofeng , Yang Chen , Li Weihua , Liu Guixia , Tang Yun 
Published: April 2024

Abstract
Absorption, distribution, metabolism, excretion and toxicity (ADMET) properties play a crucial role in drug discovery and chemical safety assessment. Built on the achievements of admetSAR and its successor, admetSAR2.0, this paper introduced the new version of the series, admetSAR3.0, as a comprehensive platform for chemical ADMET assessment, including search, prediction and optimization modules. In the search module, admetSAR3.0 hosted over 370 000 high-quality experimental ADMET data for 104 652 unique compounds, and supplemented chemical structure similarity search function to facilitate read-across. In the prediction module, we introduced comprehensive ADMET endpoints and two new sections for environmental and cosmetic risk assessments, empowering admetSAR3.0 to provide prediction for 119 endpoints, more than double numbers compared to the previous version. Furthermore, the advanced multi-task graph neural network framework offered robust and reliable support for ADMET prediction. In particular, a module named ADMETopt was added to automatically optimize the ADMET properties of query molecules through transformation rules or scaffold hopping. Finally, admetSAR3.0 provides user-friendly interfaces for multiple types of input data, such as SMILES string, chemical structure and batch molecule file, and supports various output types, including digital, chart displays and file downloads. In summary, admetSAR3.0 is anticipated to be a valuable and powerful tool in drug discovery and chemical safety assessment at http://lmmd.ecust.edu.cn/admetsar3/.
Genome-wide screening and functional validation of methylation barriers near promoters
Authors: Shu Jingmin , Jelinek Jaroslav , Chen Hai , Zhang Yan , Qin Taichun , Li Ming , Liu Li , Issa Jean-Pierre J 
Published: April 2024

Abstract
CpG islands near promoters are normally unmethylated despite being surrounded by densely methylated regions. Aberrant hypermethylation of these CpG islands has been associated with the development of various human diseases. Although local genetic elements have been speculated to play a role in protecting promoters from methylation, only a limited number of methylation barriers have been identified. In this study, we conducted an integrated computational and experimental investigation of colorectal cancer methylomes. Our study revealed 610 genes with disrupted methylation barriers. Genomic sequences of these barriers shared a common 41-bp sequence motif (MB-41) that displayed homology to the chicken HS4 methylation barrier. Using the CDKN2A (P16) tumor suppressor gene promoter, we validated the protective function of MB-41 and showed that loss of such protection led to aberrant hypermethylation. Our findings highlight a novel sequence signature of cis-acting methylation barriers in the human genome that safeguard promoters from silencing.
ProTox 3.0: a webserver for the prediction of toxicity of chemicals
Authors: Banerjee Priyanka , Kemmler Emanuel , Dunkel Mathias , Preissner Robert 
Published: April 2024

Abstract
Interaction with chemicals, present in drugs, food, environments, and consumer goods, is an integral part of our everyday life. However, depending on the amount and duration, such interactions can also result in adverse effects. With the increase in computational methods, the in silico methods can offer significant benefits to both regulatory needs and requirements for risk assessments and the pharmaceutical industry to assess the safety profile of a chemical. Here, we present ProTox 3.0, which incorporates molecular similarity and machine-learning models for the prediction of 61 toxicity endpoints such as acute toxicity, organ toxicity, clinical toxicity, molecular-initiating events (MOE), adverse outcomes (Tox21) pathways, several other toxicological endpoints and toxicity off-targets. All the ProTox 3.0 models are validated on independent external sets and have shown strong performance. ProTox envisages itself as a complete, freely available computational platform for in silico toxicity prediction for toxicologists, regulatory agencies, computational chemists, and medicinal chemists. The ProTox 3.0 webserver is free and open to all users, and there is no login requirement and can be accessed via https://tox.charite.de. The web server takes a 2D chemical structure as input and reports the toxicological profile of the compound for each endpoint with a confidence score and overall toxicity radar plot and network plot.
HDAC10 inhibition represses melanoma cell growth and BRAF inhibitor resistance via upregulating SPARC expression
Authors: Ling Hongbo , Li Yixuan , Peng Changmin , Yang Shengyu , Seto Edward 
Published: April 2024

Abstract
Secreted protein acidic and rich in cysteine (SPARC), a conserved secreted glycoprotein, plays crucial roles in regulating various biological processes. SPARC is highly expressed and has profound implications in several cancer types, including melanoma. Understanding the mechanisms that govern SPARC expression in cancers has the potential to lead to improved cancer diagnosis, prognosis, treatment strategies, and patient outcomes. Here, we demonstrate that histone deacetylase 10 (HDAC10) is a key regulator of SPARC expression in melanoma cells. Depletion or inhibition of HDAC10 upregulates SPARC expression, whereas overexpression of HDAC10 downregulates it. Mechanistically, HDAC10 coordinates with histone acetyltransferase p300 to modulate the state of acetylation of histone H3 at lysine 27 (H3K27ac) at SPARC regulatory elements and the recruitment of bromodomain-containing protein 4 (BRD4) to these regions, thereby fine-tuning SPARC transcription. HDAC10 depletion and resultant SPARC upregulation repress melanoma cell growth primarily by activating AMPK signaling and inducing autophagy. Moreover, SPARC upregulation due to HDAC10 depletion partly accounts for the resensitization of resistant cells to a BRAF inhibitor. Our work reveals the role of HDAC10 in gene regulation through indirect histone modification and suggests a potential therapeutic strategy for melanoma or other cancers by targeting HDAC10 and SPARC.
Three-year follow-up analysis of phase 1/2 study on tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma
Authors: Yonezawa Hajime , Narita Yoshitaka , Nagane Motoo , Mishima Kazuhiko , Terui Yasuhito , Arakawa Yoshiki , Asai Katsunori , Fukuhara Noriko , Sugiyama Kazuhiko , Shinojima Naoki , Aoi Arata , Nishikawa Ryo 
Published: April 2024

Abstract

Background
The ONO-4059-02 phase 1/2 study showed favorable efficacy and acceptable safety profile of tirabrutinib, a second-generation Bruton’s tyrosine kinase inhibitor, for relapsed/refractory primary central nervous system lymphoma (PCNSL). Here, we report the long-term efficacy and safety after a 3-year follow-up.

Methods
Eligible patients were aged ≥ 20 years with histologically diagnosed PCNSL and KPS of ≥ 70. Patients received oral tirabrutinib once daily at 320 or 480 mg, or 480 mg under fasted conditions.

Results
Between October 19, 2017, and June 13, 2019, 44 patients were enrolled: 33 and 9 had relapsed and refractory, respectively. The 320, 480, and 480 mg fasted groups included 20, 7, and 17 patients, respectively. The median follow-up was 37.1 months. The overall response rate was 63.6% (95% CI: 47.8–77.6) with complete response (CR), unconfirmed CR, and partial response in 9, 7, and 12 patients, respectively. The median duration of response (DOR) was 9.2 months, with a DOR rate of 19.8%; the median progression-free survival (PFS) and median overall survival (OS) were 2.9 months and not reached, respectively, with PFS and OS rates of 13.9% and 56.7%, respectively. Adverse events occurred in 38 patients (86.4%): grade ≥ 3 in 23 (52.3%) including 1 patient with grade 5 events. KPS and quality of life (QoL) scores were well maintained among patients receiving long-term treatment.

Conclusions
The results demonstrated the long-term clinical benefit of tirabrutinib, with deep and durable response in a subset of patients and acceptable safety profile, while KPS and QoL scores were maintained.