bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of iron acquisition by multiple small RNAs unravels a new role for transcriptional terminator loops in gene regulation
Authors: Flores Eugenio Solchaga , Jagodnik Jonathan , Quenette Fanny , Korepanov Alexey , Guillier Maude 
Published: January 2024

ABSTRACTSmall RNAs (sRNAs) controlling gene expression by imperfect base-pairing with mRNA(s) are widespread in bacteria and regulate multiple genes, including genes involved in iron homeostasis, through a wide variety of mechanisms. We previously showed that OmrA and OmrB sRNAs repress the synthesis of theEscherichia coliFepA receptor for iron-enterobactin complexes. We now report that five additional sRNAs, namely RprA, RybB, ArrS, RseX and SdsR, that respond to different environmental cues, also repressfepA,independently of one another. While RprA follows the canonical mechanism of pairing with the translation initiation region, repression by ArrS or RseX requires a secondary structure far upstream within the longfepA5’UTR. We also demonstrate a dual action of SdsR, whose 5’ end pairs with thefepAtranslation initiation region while its 3’ end behaves like ArrS or RseX. Strikingly, mutation analysis shows a key role for the loops of these sRNAs intrinsic terminators in the regulation. Regulation furthermore depends on both the Hfq chaperone and the RNase E endonuclease. Overall, our data strongly suggest that FepA levels must be tightly controlled under a variety of conditions, and highlight the diversity of mechanisms that underly the regulation of gene expression by sRNAs in bacteria.
Assessing the relationship between neural entrainment and altered states of consciousness induced by electronic music
Authors: Aparicio-Terrés Raquel , López-Mochales Samantha , Díaz-Andreu Margarita , Escera Carles 
Published: January 2024

ABSTRACTIn electronic music events, the driving four-on-the-floor music appears pivotal for inducing altered states of consciousness (ASCs). While various physiological mechanisms link repetitive auditory stimuli to ASCs, entrainment—a brainwave synchronization through periodic external stimuli— has garnered primary focus. However, there are no studies systematically exploring the relationship between entrainment and ASCs. In the present study, we depart from the finding that entrainment to auditory stimuli peaks for stimulation rates around 2 Hz compared to others. Twenty participants listened to six one-minute electronic music excerpts at different tempos (1.65 Hz, 2.25 Hz, and 2.85 Hz). For each excerpt, they performed cognitive tasks and reported phenomenological experiences related to ASCs through questionnaires. Brain activity was recorded with electroencephalography to assess whether a modulation in entrainment by the beat of electronic music affected objective and subjective proxies of ASCs. Our results revealed a tempo-driven entrainment modulation, peaking at 1.65 Hz. Similarly, participants’ experience of unity during listening to the music was higher for the excerpts at 1.65 Hz, yet no relationship with entrainment was found. Critically, a correlation was found between entrainment and participants’ reaction time. Further studies are granted to explore how individual traits, such as musical training, modulate the relationship.
Prediction error determines how memories are organized in the brain: a study of Pavlovian fear extinction in rats
Authors: Kennedy Nicholas G. W. , Lee Jessica C. , Killcross Simon , Westbrook Fred , Holmes Nathan M. 
Published: January 2024

AbstractHow is new information organized in memory? According to latent state theories, this is determined by the level of surprise, or prediction error, generated by the new information: small prediction error leads to updating of existing memory, large prediction error leads to encoding of a new memory. We tested this idea using a protocol in which rats were first conditioned to fear a stimulus paired with shock. The stimulus was then gradually extinguished by progressively reducing the shock intensity until the stimulus was presented alone. Consistent with latent state theories, this gradual extinction protocol (small prediction errors) was better than standard extinction (large prediction errors) in producing long-term suppression of fear responses; and the benefit of gradual extinction was due to updating of the conditioning memory with information about extinction. Thus, prediction error determines how new information is organized in memory, and latent state theories adequately describe the ways in which this occurs.
Macrophage-induced reduction of bacteriophage density limits the efficacy ofin vivopulmonary phage therapy
Authors: Zborowsky Sophia , Seurat Jérémy , Balacheff Quentin , Ecomard Solène , Minh Chau Nguyen Ngoc , Titécat Marie , Evrard Emma , Rodriguez-Gonzalez Rogelio A. , Marchi Jacopo , Weitz Joshua S. , Debarbieux Laurent 
Published: January 2024

AbstractThe rise of antimicrobial resistance has led to renewed interest in evaluating phage therapy. In murine models highly effective treatment of acute pneumonia caused byPseudomonas aeruginosarelies on the synergistic antibacterial activity of bacteriophages with neutrophils. Here, we show that depletion of alveolar macrophages (AM) shortens the survival of mice without boosting theP. aeruginosaload in the lungs. Unexpectedly, upon bacteriophage treatment, pulmonary levels ofP. aeruginosawere significantly lower in AM-depleted than in immunocompetent mice. To explore potential mechanisms underlying the benefit of AM-depletion in treated mice, we developed a mathematical model of phage, bacteria, and innate immune system dynamics. Simulations from the model fitted to data suggest that AM reduce bacteriophage density in the lungs. We experimentally confirmed that thein vivodecay of bacteriophage is faster in immunocompetent compared to AM-depleted animals. These findings demonstrate the involvement of feedback between bacteriophage, bacteria, and the immune system in shaping the outcomes of phage therapy in clinical settings.
Scaling and merging macromolecular diffuse scattering withmdx2
Authors: Meisburgera Steve P. , Andob Nozomi 
Published: January 2024

AbstractDiffuse scattering is a promising method to gain additional insight into protein dynamics from macro-molecular crystallography (MX) experiments. Bragg intensities yield the average electron density, while the diffuse scattering can be processed to obtain a three-dimensional reciprocal space map, that is further analyzed to determine correlated motion. To make diffuse scattering techniques more accessible, we have created software for data processing calledmdx2that is both convenient to use and simple to extend and modify.Mdx2is written in Python, and it interfaces withDIALSto implement self-contained data reduction workflows. Data are stored in NeXusformat for software interchange and convenient visualization.Mdx2can be run on the command line or imported as a package, for instance to encapsulate a complete workflow in a Jupyter notebook for reproducible computing and education. Here, we describemdx2version 1.0, a new release incorporating state-of-the-art techniques for data reduction. We describe the implementation of a complete multi-crystal scaling and merging workflow, and test the methods using a high-redundancy dataset from cubic insulin. We show that redundancy can be leveraged during scaling to correct systematic errors, and obtain accurate and reproducible measurements of weak diffuse signals.SynopsisMdx2is a Python toolkit for processing diffuse scattering data from macromolecular crystals. We describe multi-crystal scaling and merging procedures implemented in the latest version ofmdx2. A high-redundancy dataset from cubic insulin is processed to reveal weak scattering features.
Forced mouth opening induces post-traumatic hyperalgesia and associated peripheral sensitization after temporomandibular joints injury in mice
Authors: Alshanqiti Ishraq , Son Hyeonwi , Shannonhouse John , Hu Jiaxin , Kumari Sinu , Parastooei Ghazaal , Wang Sheng , Ro Jin Y. , Kim Yu Shin , Chung Man-Kyo 
Published: January 2024

ABSTRACTTemporomandibular disorder (TMD) is the most prevalent painful condition in the craniofacial area. The pathophysiology of TMD is not fully understood, and it is necessary to understand pathophysiology underlying painful TMD conditions to develop more effective treatment methods. Recent studies suggested that external or intrinsic trauma to TMJ is associated with chronic TMD in patients. Here, we investigated the effects of the TMJ trauma through forced-mouth opening (FMO) in mice to determine pain behaviors and peripheral sensitization of trigeminal nociceptors. FMO increased mechanical hyperalgesia assessed by von Frey test, spontaneous pain-like behaviors assessed by mouse grimace scale, and anxiety-like behaviors assessed by open-field test. In vivo GCaMP Ca2+imaging of intact trigeminal ganglia (TG) showed increased spontaneous Ca2+activity and mechanical hypersensitivity of TG neurons in the FMO compared to the sham group. Ca2+responses evoked by cold, heat, and capsaicin stimuli were also increased. FMO-induced hyperalgesia and neuronal hyperactivities were not sex dependent. TG neurons sensitized following FMO were primarily small to medium-sized nociceptive afferents. Consistently, most TMJ afferents in the TG were small-sized peptidergic neurons expressing calcitonin gene-related peptides, whereas nonpeptidergic TMJ afferents were relatively low. FMO-induced intraneural inflammation in the surrounding tissues of the TMJ indicates potentially novel mechanisms of peripheral sensitization following TMJ injury. These results suggest that the TMJ injury leads to persistent post-traumatic hyperalgesia associated with peripheral sensitization of trigeminal nociceptors.
Mitochondria-containing extracellular vesicles from mousevs. human brain endothelial cells for ischemic stroke therapy
Authors: Dave Kandarp M. , Venna Venugopal R. , Rao Krithika S. , Stolz Donna B. , Brady Bodhi , Quaicoe Victoria A. , Maniskas Michael E. , Hildebrand Ella E. , Green Dawson , Chen Mingxi , Milosevic Jadranka , Zheng Si-yang , Shiva Sruti S. , McCullough Louise D. , Manickam Devika S 
Published: January 2024

AbstractIschemic stroke-induced mitochondrial dysfunction in the blood-brain barrier-forming brain endothelial cells (BECs) results in long-term neurological dysfunction post-stroke. We previously data from a pilot study whereintravenousadministration of human BEC (hBEC)-derived mitochondria-containing extracellular vesicles (EVs) showed a potential efficacy signal in a mouse middle cerebral artery occlusion (MCAo) model of stroke. Wehypothesizedthat EVs harvested from donor species homologous to the recipient species (e.g.,mouse) may improve therapeutic efficacy, and therefore, use of mouse BEC (mBEC)-derived EVs may improve post-stroke outcomes in MCAo mice.We investigated potential differences in the mitochondria transfer of EVs derived from the same species as the recipient cell (mBEC-EVs and recipient mBECs or hBECs-EVs and recipient hBECs)vs. cross-species EVs and recipient cells (mBEC-EVs and recipient hBECs orvice versa). Our results showed that while both hBEC- and mBEC-EVs transferred EV mitochondria, mBEC-EVs outperformed hBEC-EVs in increasing ATP levels and improved recipient mBEC mitochondrial function via increasing oxygen consumption rates. mBEC-EVs significantly reduced brain infarct volume and neurological deficit scores compared to vehicle-injected MCAo mice. The superior therapeutic efficacy of mBEC-EVs in a mouse MCAo stroke support the continued use of mBEC-EVs to optimize the therapeutic potential of mitochondria-containing EVs in preclinical mouse models.Graphical Abstract
Structural basis of respiratory complexes adaptation to cold temperatures
Authors: Shin Young-Cheul , Latorre-Muro Pedro , Djurabekova Amina , Zdorevskyi Oleksii , Bennett Christopher F. , Burger Nils , Song Kangkang , Xu Chen , Sharma Vivek , Liao Maofu , Puigserver Pere 
Published: January 2024

AbstractIn response to cold, mammals activate brown fat for respiratory-dependent thermogenesis reliant on the electron transport chain (1, 2). Yet, the structural basis of respiratory complex adaptation to cold remains elusive. Herein we combined thermoregulatory physiology and cryo-EM to study endogenous respiratory supercomplexes exposed to different temperatures. A cold-induced conformation of CI:III2(termed type 2) was identified with a ∼25° rotation of CIII2around its inter-dimer axis, shortening inter-complex Q exchange space, and exhibiting different catalytic states which favor electron transfer. Large-scale supercomplex simulations in lipid membrane reveal how unique lipid-protein arrangements stabilize type 2 complexes to enhance catalytic activity. Together, our cryo-EM studies, multiscale simulations and biochemical analyses unveil the mechanisms and dynamics of respiratory adaptation at the structural and energetic level.
Elucidation of neuronal activity in mouse models of TMJ injury byin vivoGCaMP Ca2+imaging of intact trigeminal ganglion neurons
Authors: Son Hyeonwi , Shannonhouse John , Zhang Yan , Gomez Ruben , Chung Man-Kyo , Kim Yu Shin 
Published: January 2024

AbstractPatients with temporomandibular disorders (TMD) typically experience facial pain and discomfort or tenderness in the temporomandibular joint (TMJ), causing disability in daily life. Unfortunately, existing treatments for TMD are not always effective, creating a need for more advanced, mechanism-based therapies. In this study, we usedin vivoGCaMP3 Ca2+imaging of intact trigeminal ganglia (TG) to characterize functional activity of the TG neuronsin vivo, specifically in TMJ animal models. This system allows us to observe neuronal activity in intact anatomical, physiological, and clinical conditions and to assess neuronal function and response to various stimuli. We observed a significant increase in spontaneously and transiently activated neurons responding to mechanical, thermal, and chemical stimuli in the TG of forced mouth open (FMO) mice. An inhibitor of the CGRP receptor significantly attenuated FMO-induced facial hypersensitivity. In addition, we confirmed the attenuating effect of CGRP antagonist on FMO-induced sensitization byin vivoGCaMP3 Ca2+imaging of intact TG. Our results contribute to unraveling the role and activity of TG neurons in the TMJ pain animal models of TMD, bringing us closer understanding the pathophysiological processes underlying TMD. Our study also illustrates the utility ofin vivoGCaMP3 Ca2+imaging of intact TG for studies aimed at developing more targeted and effective treatments for TMD.
Testosterone-Induced Metabolic Changes in Seminal Vesicle Epithelial cells Alter Plasma Components to Enhance Sperm Motility
Authors: Yamanaka Takahiro , Xiao Zimo , Tsujita Natsumi , Awad Mahmoud , Umehara Takashi , Shimada Masayuki 
Published: January 2024

AbstractMale factors account for almost half of the causes of infertility. In rodents and humans, most of the components of semen are supplied by the seminal vesicles, and they support male reproductive ability, but there are many unknown details. In this study, the metabolic changes in the seminal vesicle epithelial cells were focused on, and the mechanisms by which testosterone affected the seminal plasma composition were investigated. A factor improving the linear motility of sperm was secreted from the seminal vesicles, and it was produced in an androgen-dependent manner. Bioassays, gene expression, and flux analysis studies demonstrated that testosterone promotes glucose uptake in seminal vesicle epithelial cells via GLUT4, resulting in fatty acid synthesis. ACLY was a critical factor in this metabolic change, which produced fatty acid, especially oleic acid. In conclusion, the critical role of testosterone-induced metabolic changes in the seminal vesicles is to ensure the synthesis of fatty acid. These findings provide new understanding the male fertility mechanisms and may perspective for the development of potential biomarkers of male fertility and advance in the treatment of male infertility.
Stimulation of NCAM1-14.3.3.ζδ-derived Peptide Interaction Fuels Angiogenesis and Osteogenesis in Ageing
Authors: Yesin Taha Kadir , Liu Hanyu , Ding Zhangfan , Singh Amit , Tian Qi , Zhang Yuheng , Borah Biswajyoti , Chen Junyu , Kusumbe Anjali P. 
Published: January 2024

AbstractThe skeletal structure and bone marrow endothelium collectively form a critical functional unit essential for bone development, health, and aging. At the core of osteogenesis and bone formation lies the dynamic process of angiogenesis. In this study, we reveal a potent new endogenous anabolic NCAM1-14.3.3.ζδ-derived-Peptide interaction, which stimulates bone angiogenesis and osteogenesis during homeostasis, aging, and age-related bone diseases. Employing high-resolution imaging and inducible cell-specific mouse genetics, our results elucidate the pivotal role of the NCAM1-14.3.3.ζδ-derived-Peptide interaction in driving the expansion of Clec14a+ angiogenic endothelial cells. Notably, Clec14a+ endothelial cells express key osteogenic factors. The NCAM1-14.3.3.ζδ-derived-Peptide interaction in osteoblasts drives osteoblast differentiation, ultimately contributing to the genesis of new bone. Moreover, the NCAM1-14.3.3.ζδ-derived-Peptide interaction leads to a reduction in bone resorption. In age-associated vascular and bone loss diseases, stimulating the NCAM1-14.3.3.ζδ-derived-Peptide interaction not only promotes angiogenesis but also reverses bone loss. Consequently, harnessing the endogenous anabolic potential of the NCAM1-14.3.3.ζδ-derived-Peptide interaction emerges as a promising therapeutic modality for managing age-related bone diseases.
SAM-DNMT3A, a strategy for induction of genome-wide DNA methylation, identifies DNA methylation as a vulnerability in ER-positive breast cancers
Authors: Hosseinpour Mahnaz , Malaver-Ortega Luis , Perlaza-Jimenez Laura , Joo Jihoon E. , Liu Ling , Caldon Elizabeth C. , Dugué Pierre-Antoine , Dowty James G. , Southey Melissa C. , Rosenbluh Joseph 
Published: January 2024

AbstractDNA methylation is an epigenetic mark that plays a critical role in regulation of gene expression. DNA methylase (DNMT) inhibitors, inhibit global DNA methylation, and have been a key tool in studies of DNA methylation in healthy or disease conditions. A major bottleneck is the lack of tools to induce global DNA methylation. Here, we engineered a CRISPR based approach, that was initially designed, to enable site specific DNA methylation. Using the synergistic activation mediator (SAM) system, we unexpectedly found that regardless of the targeted sequence any sgRNA induced global genome-wide DNA methylation. We termed this new method SAM-DNMT3A and show that induction of global DNA methylation is a unique vulnerability in ER-positive breast cancer suggesting a therapeutic approach. Our findings highlight the need of caution when using CRISPR based approaches for inducing DNA methylation and demonstrate a new method for global induction of DNA methylation.
WITHDRAWN: Development and external validation of a practical diagnostic support tool, ‘ABC 2-Screener’, to predict sarcopenia among patients on maintenance haemodialysis: A multicentre cross-sectional study
Authors: Matsunami Masatoshi , Aita Tetsuro , Kamitani Tsukasa , Munakata Yu , Kawaji Atsuro , Kuji Hiroshi , Suzuki Tomo , Kurita Noriaki 
Published: January 2024

Withdrawal StatementThe authors have withdrawn their manuscript owing to uncorrectable data errors which were discovered after posting. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Key role of vimentin in the organization of the primary cilium
Authors: Lalioti Vasiliki , Moneo-Corcuera Diego , Pérez-Sala Dolores 
Published: January 2024

AbstractWe previously reported the presence of the intermediate filament vimentin at the primary cilium of lung cancer epithelial cells. In this study we further demonstrate that vimentin is intimately intertwined with acetylated tubulin at this structure. Interestingly, although vimentin can be detected along the whole length of the primary cilium, phospho-serine 56 vimentin is found particularly enriched at its basal region in A549 lung cancer cells. Vimentin appears to play a pivotal role in ciliogenesis, since its depletion in MEF or in A549 cells results in a lower proportion of cells displaying primary cilia and recognizable basal bodies. Furthermore, the detectable cilia in vimentin depleted cells are shorter. In addition, the centriolar structure appears disrupted in vimentin deficient cells, as indicated by an abnormal distribution of γ- and acetylated tubulin. Moreover, these cells display a defective organization of the pericentriolar material, characterized by a marked decrease in the levels of pericentrin and a diffuse distribution of Rab11. Taken together, our results show that vimentin is present at the primary cilium and suggest that it plays an important role in cilium structure and biogenesis, since its depletion leads to marked morphological defects and altered organization of key elements of this structure.
IER3IP1-mutations cause microcephaly by selective inhibition of ER-Golgi transport
Authors: Anitei Mihaela , Bruno Francesca , Valkova Christina , Dau Therese , Cirri Emilio , Lascano Iván Mestres , Calegari Federico , Kaether Christoph 
Published: January 2024

AbstractMutations in theIER3IP1(Immediate Early Response-3 Interacting Protein 1) gene can give rise to MEDS1 (Microcephaly with Simplified Gyral Pattern, Epilepsy, and Permanent Neonatal Diabetes Syndrome-1), a severe condition leading to early childhood mortality. The small endoplasmic reticulum (ER)-membrane protein IER3IP1 plays a non-essential role in ER-Golgi transport. Here, we employed secretome and cell-surface proteomics to demonstrate that the absence of IER3IP1 or the presence of the pathogenic p.L78P mutation results in the retention of specific cell-surface receptors and secreted proteins crucial for neuronal migration within the ER. This phenomenon correlates with the distension of ER membranes and increased lysosomal activity. Notably, the trafficking of cargo receptor ERGIC53 and KDEL-receptor 2 is compromised, with the latter leading to the anomalous secretion of ER-localized chaperones. Our investigation extended to in-utero knock-down ofIer3ip1in mouse embryo brains, revealing a morphological phenotype in newborn neurons. In summary, our findings provide insights into how the loss or mutation of a 10 kDa small ER-membrane protein can cause a fatal syndrome.