bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isotopic tracing inMycobacterium tuberculosis-infected alveolar epithelial cells indicates metabolic specificity to their virulence and drug-resistance status
Authors: Akram Subia , Masakapalli Shyam Kumar , Nanda Ranjan Kumar 
Published: December 2024

SummaryMycobacterium tuberculosis(Mtb), the causative organism of tuberculosis (TB), infects different host cells; however, studies on its metabolic impact on the type 2 alveolar epithelial cells are limited. In this study, comparative metabolic insights of A549 cells infected with laboratory (H37RV, H37Ra) and clinical isolates (drug-resistant: S6, S11 and sensitive: S4, S5) were derived from read out of the13C-based proteinogenic amino acid kinetics. Mtb H37Rv (virulent) exhibited higher growth kinetics within A549 cells compared to H37Ra (avirulent), whereas drug-resistant clinical isolate S6 showed the highest intracellular growth. The viability of H37Rv-infected A549 cells was significantly low. Interestingly, the drug-resistant clinical Mtb isolates maintained better cell viability over time. A [13C6] glucose tracer and mass isotopomer distributions revealed that A549 cells infected with virulent Mtb strains exhibited higher dependency on the central carbon metabolism like glycolysis, the pentose phosphate pathway and the tricarboxylic acid cycle forde novoamino acid biosynthesis. Drug-resistant Mtb isolates infected A549 cells showed robust13C incorporation in the proteinogenic Threonine, Methionine and Lysine, derived from the tricarboxylic acid cycle. A549 cells infected with Mtb, irrespective of their drug resistance status, showed13C incorporation in the essential amino acids (lysine, methionine, threonine, valine), underlining the dependencies of the pathogen on thede novohost metabolic precursors. These findings elucidate the importance of deciphering the strain-specific host-pathogen metabolic interactions to develop targeted therapies against drug-resistant Mtb infections.
CD226+adipose tissue macrophages arise from MDP-derived monocytes and regulate lipid metabolism
Authors: Gallerand Alexandre , Caillot Zakariya , Terekhova Marina , Castiglione Alexia , Leporati Lorlana , Giacchero Margaux , Pilot Thomas , Chang Michael , Dolfi Bastien , Zair Fairouz N. , Goës Eloïse , Bennetot Audrey , Mlamla Zandile , Mass Elvira , Ginhoux Florent , Voehringer David , Mack Matthias , Dombrowicz David , Williams Jesse W. , Masson David , Artyomov Maxim N. , Bertola Adeline , Ivanov Stoyan 
Published: December 2024

AbstractMacrophages are innate immune cells present in all tissues, in which they participate in immune responses and maintenance of tissue homeostasis. They develop either from embryonic precursors or from circulating monocytes, and their functions are in part dictated by their origin. We previously observed robust monocyte recruitment and contribution to the macrophage pool in brown adipose tissue. In particular, monocytes were predicted to give rise to two phenotypically distinct macrophage subsets identifiable by CD206 or CD226 expression. In the present study, we investigated monocyte differentiation pathways in brown adipose tissue and the function of monocyte-derived macrophages. We found that bone marrow monocytes highly contributed to the CD226+macrophage population while the CD206+population contained mainly yolk sac-derived cells. Fate mapping analysis revealed a low contribution of GMP- and a high contribution of MDP-derived monocytes to the CD226+macrophage subset. Importantly, adoptive transfer experiments demonstrate that MDP- but not GMP-derived monocytes are pre-conditioned to give rise to CD226+macrophages. Using meta-analysis of single cell RNA-sequencing data, we found that MDP-derived CD226+macrophages were present in several tissues including peritoneal cavity, adrenal glands and all adipose depots, with a particular enrichment in beige and brown fat. A similar macrophage subset was identified in humans. Functionally, while depletion of CD206+macrophages using anti-CD115 blocking antibodies led to decreased adipose triglyceride content, genetic depletion of CD226+macrophages caused the opposite phenotype. We thus identify CD226+MDP-derived macrophages as a new myeloid cell type conserved across tissues and tied to lipid metabolism homeostasis.
Narcissistic and Antisocial Personality Traits are both encoded in the Triple Network: Connectomics evidence
Authors: Jornkokgoud Khanitin , Bakiaj Richard , Wongupparaj Peera , Job Remo , Grecucci Alessandro 
Published: December 2024

AbstractThe neural bases of narcissistic and antisocial traits are still under debate. One intriguing question is whether these traits are encoded within the so-called triple network e.g. the default mode (DMN), salience (SN), and fronto-parietal (FPN) networks, and whether these traits affect the same networks in a similar manner. Connectome-based analyses were conducted on resting-state scans from 183 participants, examining regional and global graph-theoretic metrics in the DMN, SN, and FPN, with the visual and sensorimotor networks as controls. Our findings revealed a clear involvement of the triple network in narcissistic and antisocial traits, confirming a shared neural substrate for the two traits. Both traits were negatively predicted by the anterior cingulate cortex of the SN, possibly indicating less awareness of dangers and more proneness to engage in risky behaviors. Additionally, both traits were positively predicted by the lateral prefrontal cortex of the FPN, suggesting augmented strategic thinking to manipulate others and increased planning skills to achieve personal goals. Besides similarities, there were also some differences. Specific hubs of the DMN were positively associated with narcissism but negatively related with antisocials, possibly explaining their differences in self-reflection and thinking about the self, largely present in the former, but usually reduced in the latter. These results extend previous findings on the involvement of the triple network in personality disorders and suggest both common and different mechanisms underlying narcissistic and antisocial traits. As such, these findings could pave the way for developing potential biomarkers of personality pathology and identify neurostimulation intervention targets.
PTX3 Governs Fibroblast-Epithelial Dynamics in Lung Injury and Repair
Authors: Bammert Marie-Therese , Kollak Ines , Hoffmann Jan , Peter Eva , Schlüter Holger , Li Jun , Campos Alexandre R. , Viollet Coralie , Gantner Florian , Lizé Muriel , Thomas Matthew J. , Le Huy Q. 
Published: December 2024

AbstractDysfunctional interactions between fibroblasts and epithelial cells contribute to the progression of chronic lung diseases, including idiopathic pulmonary fibrosis (IPF). In this study, we utilized a coculture model of human small airway epithelial cells and fibroblasts to investigate intercellular communication during disease progression. Our transcriptomic and proteomic profiling reveal that fibroblasts repair epithelial cells in acute injury by boosting epithelial fatty acid metabolism; conversely, they exacerbate epithelial damage in chronic injury scenarios. By delineating regulators involved in these responses, we identified pentraxin 3 (PTX3) as a key antifibrotic factor secreted by fibroblasts in response to acute epithelial injury. Importantly, PTX3 levels are decreased in bronchoalveolar lavage (BAL) samples from IPF patients compared to non-fibrotic controls, indicating a potential link between diminished PTX3 levels and fibrosis progression. Furthermore, adding PTX3 to chronically injured epithelial-fibroblast cocultures mitigated the pro-fibrotic response and restored the epithelial barrier integrity. These findings highlight the dual roles of fibroblasts and the critical function of PTX3 in lung injury and repair, offering insights for therapeutic strategies.
Identification of novel inhibitors targeting serine acetyltransferase fromNeisseria gonorrhoeae
Authors: Oldham Keely E.A. , Jiao Wanting , Prentice Erica , Hicks Joanna L. 
Published: December 2024

AbstractNeisseria gonorrhoeaeis an obligate human pathogen and the etiological agent of the sexually transmitted infection, gonorrhoea. The rapid emergence of extensively antimicrobial-resistant strains, including those resistant to all frontline antibiotics, has led toN. gonorrhoeaebeing labelled a priority pathogen by the World Health Organization, highlighting the need for new antimicrobial treatments. Given its absence in humans, targetingde novocysteine biosynthesis has been identified as a promising avenue for developing new antimicrobials against drug-resistant bacteria. The biosynthesis of cysteine is catalyzed by two enzymes; serine acetyltransferase (SAT/CysE) which catalyzes the first step andO-acetylserine sulfhydrylase (OASS/CysK) that catalyzes the second step incorporating sulfur to form L-cysteine. CysE is reported to be essential for bacterial survival in several bacterial pathogens includingN. gonorrhoeae. Here, we have conducted virtual inhibitor screening of commercially available compound libraries against SAT fromN. gonorrhoeae(NgSAT). We have identified a hit compound with an IC50of 13.9 µM and analyzed its interactions with the enzyme’s active site. This provides a platform for the identification and development of novel SAT inhibitors to combat drug-resistant bacterial pathogens.
Simple One-step Vial-based Pretreatment for Deep Single-cell Proteomics and Its Application to Oocyte Aging
Authors: Zhang Hui , Zhang Hailu , Huang Chuanxi , Zeng Qing , Tian Chunyan , He Fuchu , Yang Yun 
Published: December 2024

ABSTRACTSingle-cell proteomics is a pivotal technology for studying cellular phenotypes, offering unparalleled insights into cellular heterogeneity and dynamic functions. Technical improvement in mass spectrometry instrument and sample preparation has made single-cell proteomics feasible in recent years. Yet, developing a simple and robust sample preparation method to enable deep proteomics profiling of single cells remains a significant challenge. Herein, we developed a simple one-step vial-based pretreatment (SOViP) for deep label-free single-cell proteomics. SOViP integrates all sample preparation procedures into a single step in autosampler vials, yet it is highly efficient and high-throughput. SOViP can be finished within ∼2 h, with hands-on time limited to merely a few minutes. We show that on average over 6,500 can be quantified from a single mouse oocyte using SOViP. In total 6,983 protein groups were identified from single mouse oocytes across an entire reproductive lifespan, offering a valuable proteomics resource for oocyte aging. Unique molecular characteristics of oocytes at different ages were revealed, and a classifier consisting of ten proteins demonstrated accurate age-group classification and fertility-level prediction. Although demonstrated using mouse oocytes in this study, SOViP is adaptable to rare cell samples and other large cells, including follicles and preimplantation embryo cells, among others.
A novelCandida glabrataprotein regulated by mating signalling pathway shapes inter-species interaction
Authors: Parnandi Venkata Anand , Trivedi Parth M. , Panchal Harshita , Patkar Rajesh N. 
Published: December 2024

AbstractDuring mixed-species invasive candidiasis - an emerging threat in healthcare - presence ofCandida albicansis near-essential for host colonisation byC. glabrata. However, the molecular communication underlying such intriguing inter-species interaction is largely unexplored. Here, we show thatC. glabratasecretes a unique small protein Yhi1 that induces hyphal growth inC. albicans, which is essential for host tissue invasion. Notably, this Yhi1-based inter-species interaction is specific toC. glabrataandC. albicans, when compared with other common species ofCandida.Our structure-function analyses reveal a novel functional pentapeptide motif (AXVXH) required for the function of Yhi1. Interestingly, Yhi1 expression and efflux are regulated through the mating MAPK signalling pathway and the pheromone transporterCgSte6, respectively, inC. glabrata, despite its preferred asexual reproduction. Our findings shed light on howC. glabratamating signalling pathway is repurposed to interact withC. albicans, and highlight the potential of Yhi1 as a biomarker and a template for a synthetic novel antifungal peptide.
Early-life stress impairs development of functional interactions and neuronal activity within prefrontal-amygdala networksin vivo
Authors: Donati Angelica , Vedele Francescangelo , Hartung Henrike 
Published: December 2024

AbstractEarly-life stress (ELS), such as parental neglect or abuse, predisposes an individual to develop mental disorders. Disease hallmarks include heightened amygdala reactivity and impaired prefrontal cortex-amygdala functional interactions, already during childhood and adolescence. However, which cellular and circuit mechanisms underlie these hallmarks, as well as the altered developmental trajectory of prefrontal-amygdala networks, is poorly understood. Here we performed simultaneousin vivolocal-field potential and multi-unit recordings under light urethane anaesthesia in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) of male and female juvenile or adolescent mice, exposed to a resource scarcity model of ELS. We find a developmentally transient low-theta (3-5 Hz) oscillatory hypercoupling within mPFC-BLA networks in juvenile ELS males which seems to result from a precocious development of coupling strength after ELS. In the mPFC, neuronal spiking activity was decreased in juvenile males and the local theta entrainment of spike firing disrupted. In BLA, both sexes showed an increase in firing activity in a subpopulation of neurons after ELS, also confirmed by an increase in ΔFosB-positive neurons in BLA, which we identified to be non-GABAergic. Directed interactions, i.e. the ability to entrain spike firing in mPFC to the theta rhythm in BLA and vice versa, were also impaired predominantly in juvenile males after ELS, while females showed a milder phenotype. These early sex-dependent impairments in the functional development of prefrontal-amygdala circuits may promote abnormal fear learning and anxiety after ELS and may predispose to a disease phenotype later on.
A major entomoparasite interferes with Chikungunya transmission byAedes albopictus
Authors: Martin Edwige , Chanfi An-nah , Viginier Barbara , Raquin Vincent , Moro Claire Valiente , Minard Guillaume 
Published: December 2024

AbstractThe Asian tiger mosquito,Aedes albopictus, spreads diseases like Chikungunya and has caused outbreaks worldwide. Studies show that mosquitoes-associated microbes can affect how well they spread diseases. One of those microbes, the parasiteAs. taiwanensis, is common in older mosquito populations but rare in newer ones. We found that this parasite slows down the spread of Chikungunya within the mosquito and decreases its transmission rate by half. Unparasitized mosquitoes spread the virus more easily, suggesting that changes in mosquito microbes could impact disease outbreaks and public health.
Revealing rhythm categorization in human brain activity
Authors: Barbero Francesca M. , Lenc Tomas , Jacoby Nori , Polak Rainer , Varlet Manuel , Nozaradan Sylvie 
Published: December 2024

ABSTRACTHumans across cultures show an outstanding capacity to perceive, learn, and produce musical rhythms. These skills rely on mapping the infinite space of possible rhythmic sensory inputs onto a finite set of internal rhythm categories. What are the brain processes underlying rhythm categorization? We used electroencephalography (EEG) to measure brain activity as human participants listened to a continuum of rhythmic sequences characterized by repeating patterns of two inter-onset intervals. Using frequency and representational similarity analyses, we show that brain activity does not merely track the temporal structure of rhythmic inputs, but, instead, automatically produces categorical representation of rhythms. Surprisingly, despite this automaticity, these rhythm categories do not arise in the earliest stages of the ascending auditory pathway, but show strong similarity between implicit neural and overt behavioral responses. Together, these results and methodological advances constitute a critical step towards understanding the biological roots and diversity of musical behaviors across cultures.
BEVA2.0: Modular Assembly of Golden Gate-Compatible Vectors with Expanded Utility for Genetic Engineering
Authors: Geddes Barney A. , Williamson Riley , Schumacher Jake , Ardi Ahmad , Levin Garrett , Červenka Emily , Huang Rui , diCenzo George C. 
Published: December 2024

AbstractThis expansion for the modular vector assembly platform BEVA (Bacterial Expression Vector Archive) introduces 11 new BEVA parts including two new cloning site variants, two new antibiotic resistance modules, three new origins of replication, and four new accessary modules. As a result, the modular system is now doubled in size and expanded in its capacity to produce diverse replicating plasmids. Furthermore, it is now amenable to genetic engineering methods involving genome-manipulation of target strains through deletions or integrations. In addition to introducing the new modules, we provide several BEVA-derived Golden Gate cloning plasmids that are used to validate parts and that may be useful for genetic engineering of proteobacteria and other bacteria. We also introduce new parts to allow compatibility with the CIDAR MoClo parts libraries.
Rational engineering of allosteric protein switches byin silicoprediction of domain insertion sites
Authors: Wolf Benedict , Shehu Pegi , Brenker Luca , von Bachmann Anna , Kroell Ann-Sophie , Southern Nicholas , Holderbach Stefan , Eigenmann Joshua , Aschenbrenner Sabine , Mathony Jan , Niopek Dominik 
Published: December 2024

AbstractDomain insertion engineering is a powerful approach to juxtapose otherwise separate biological functions, resulting in proteins with new-to-nature activities. A prominent example are switchable protein variants, created by receptor domain insertion into effector proteins. Identifying suitable, allosteric sites for domain insertion, however, typically requires extensive screening and optimization.We present ProDomino, a novel machine learning pipeline to rationalize domain recombination, trained on a semi-synthetic protein sequence dataset derived from naturally occurring intradomain insertion events. ProDomino robustly identifies domain insertion sites in proteins of biotechnological relevance, which we experimentally validated inE. coliand human cells. Finally, we employed light- and chemically regulated receptor domains as inserts and demonstrate the rapid, model-guided creation of potent, single-component opto- and chemogenetic protein switches. These include novel CRISPR-Cas9 and -Cas12a variants for inducible genome engineering in human cells. Our work enables one-shot domain insertion engineering and substantially accelerates the design of customized allosteric proteins.
Generation of iPSC line ERCi004-A from human dermal fibroblasts of a patient with maturity-onset diabetes of the young type 3 caused by a heterozygous mutation in theHNF1Agene
Authors: Bastrich Asya , Antonov Daniil , Podzhilkova Aleksandra , Petrova Darya A. , Pylina Svetlana V. , Laptev Dmitriy N. , Sechko Elena A. , Kuznetsov Sergey N. , Vetchinkina Ekaterina A. , Mokrysheva Natalia G. 
Published: December 2024

AbstractMaturity-onset diabetes of the young type 3 (MODY3) disorder is characterized by an autosomal dominant type of inheritance and highly heterogeneous clinical phenotype influenced by type and position of mutation in theHNF1Agene. We reprogrammed dermal fibroblasts derived from a patient with MODY3 carrying a heterozygous mutation in the site encoding the transactivation domain of the HNF1A protein (c. 864delGinsCC, p.Gly292ArgfsTer25) into iPSCs using transfection with self-replicating RNA vector. Obtained iPSCs (ERCi004-A line) proliferate in dense monolayer cell colonies, have a normal karyotype (46,XX), express pluripotency markers (OCT4, SOX2, TRA-1-60). The functional pluripotency of iPSCs was confirmed by their ability to form embryoid bodies and differentiate into the three germ layers (ecto-, endo-, and mesoderm). Sanger sequencing of iPSCs confirmed the presence of pathogenic heterozygous mutation in theHNF1Agene. This cell line could be useful to modeling of MODY3 pathology to improve understanding of the mechanism of the transactivation domain mutation, as well as a potential source for autologous cell-based therapy.
HIV-1 single transcription start site mutants display complementary replication functions that are restored by reversion
Authors: GC K. , Lesko S. , Emery A. , Burnett C. , Gopal K. , Clark S. , Swanstrom R. , Sherer N.M. , Telesnitsky A. , Kharytonchyk S. 
Published: December 2024

AbstractHIV-1 transcription initiates at two positions, generating RNAs with eithercap1G orcap3G 5′ ends. The replication fates of these RNAs differ, with viral particles encapsidating almost exclusivelycap1G RNAs andcap3G RNAs retained in cells where they are enriched on polysomes and among spliced viral RNAs. Here, we studied replication properties of virus promoter mutants that produced only one RNA 5′ isoform or the other: separately, in combination, and during spreading infection. Results showed that either single start RNA could serve as both mRNA and genomic RNA when present as the only form in cells, althoughcap3G RNA was more efficiently translated and spliced whilecap1G RNA was packaged into nascent virions slightly better than RNAs from the parental virus. When co-expressed from separate vectors,cap1G RNA was preferentially packaged into virions. During spreading infectioncap1G-only virus displayed only minor defects butcap3G-only virus showed severe replication delays in both the highly permissive MT-4 cell line and in primary human CD4+ T cells. Passage ofcap3G-only virus yielded revertants that replicated as well as the twinned (cap1G+cap3G) transcription start site parent. These revertants displayed restored packaging and splicing levels and had regained multiple transcription start site use.ImportanceHIV-1 generates two RNAs during its replication that differ by only two nucleotides in length. Despite this very minor difference, the RNAs perform different and complementary replication functions. When mutants that expressed only one RNA were forced to revert, they regained functions associated with the second RNA.