bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing information extraction from field potentials in electrophysiology studies
Authors: Akella Shailaja , Principe Jose C. 
Published: November 2024

AbstractMulti-channel recordings from the brain serve as the primary approach to address various mechanistic and behavioral questions about neural activity and the underlying circuitry. While electrodes can detect neural activity at a distance from their source generators, activity from other concurrently active neural sources is also volume conducted to the electrodes, thus creating linear dependencies among the channels. These dependencies pose challenges in discerning specific communication patterns between different neuronal populations, and their behavioral implications. In this study, we demonstrate the capability of a marked point process (MPP) representation of channel activity, focusing on oscillatory bursts, to curtail the effects of volume conduction noise. By characterizing the localized spectral information within oscillatory bursts, we achieved a∼45% reduction in channel correlations across three recording modalities of field potentials (electroencephalography, electrocorticography, and local field potentials). We further provide evidence that the implemented sparse representation preserves both behavioral and causal information in the signal. We illustrate our findings with two examples: 1) retention of finger-level movement information in field potentials recorded from humans, demonstrated using a simple online classifier, and 2) retention of top-down connectivity information between the prefrontal and motor cortices of behaving rats. Overall, our results underscore the novelty of using a marked point process representation of oscillatory bursts to concisely encode behavioral and connectivity information while attenuating the effects of volume conduction from the causal signal sources.Author summaryMulti-channel recordings from the brain are critical to understanding how different brain regions communicate and drive behavior. However, the electrodes that detect neural activity also pick up signals from other active neural sources, leading to misleading linear dependencies among the channels. In our study, we present a novel approach using a marked point process (MPP) representation of channel activity using oscillatory bursts, to minimize the interference caused by volume conduction noise. By isolating the spectral characteristics within these oscillatory bursts, we achieved a∼45% reduction in channel correlations across three different types of field potential recordings: electroencephalography (EEG), electrocorticography (ECoG), and local field potentials (LFPs). Importantly, our method not only reduces noise but also retains critical behavioral and causal information in the neural signals. Our findings reveal that a marked point process representation of oscillatory bursts provides a more precise and noise-resilient representation of neural activity. This advancement has significant implications for both understanding brain function and improving the accuracy of brain-machine interfaces.
sRNA-mediated crosstalk between cell wall stress and galactose metabolism inStaphylococcus aureus
Authors: Germain Maëliss , Robin Hugo , Huyen Kim Boi Le , Massier Sébastien , Nalpas Nicolas , Hardouin Julie , Bouloc Philippe , Rouillon Astrid , Chabelskaya Svetlana 
Published: November 2024

ABSTRACTStaphylococcus aureusis an opportunistic pathogen responsible for a wide range of diseases in humans. During infections, this bacterium is exposed to various stresses that target its cell wall, such as oxidative or acid environments as well as various cell wall-acting antimicrobials.S. aureushas effective regulatory systems for responding to environmental stresses enabling the expression of factors necessary for its survival. Bacterial small RNAs (sRNAs) play a crucial role in this adaptation process. In this study, we show that RsaOI, anS. aureussRNA, accumulates under acid stress conditions. This response is mediated via the two-component system VraSR, which is associated with the cell wall damage response. As a component of the VraSR regulon, RsaOI contributes to the survival ofS. aureusunder acid stress and affects its susceptibility to glycopeptide antibiotics. Our findings reveal that RsaOI targetslacABCDFEGoperon, which encodes components of tagatose pathway, a unique mechanism responsible for galactose metabolism inS. aureus. By antisense base pairing near the ribosome-binding site oflacD, RsaOI inhibits the expression of this gene, encoding tagatose-6-phosphate aldolase. This regulation disrupts the tagatose pathway, impairing galactose utilization inS. aureus. These findings highlight the role of RsaOI in the mediation between cell wall stress responses and specific metabolic pathway.
High-Throughput Screening Reveals Potential Inhibitors Targeting Trimethoprim-Resistant DfrA1 Protein inKlebsiella pneumoniaeandEscherichia coli
Authors: Hasnat Soharth , Rahman Soaibur , Alam Meherun Binta , Suin Farha Mohi , Yeasmin Farzana , Suha Tanjila , Supty Nahuna Tanjin , Sabila Sal , Chowdhury Animesh , Shahinuzzaman A.D.A. , Mahbub M Murshida , Hoque M. Nazmul , Islam Tofazzal 
Published: November 2024

AbstractThe DfrA1 protein provides trimethoprim resistance in bacteria, especiallyKlebsiella pneumoniaeandEscherichia coli, by modifying dihydrofolate reductase, which reduces the binding efficacy of the antibiotic. Thus, this study aimed to identify inhibitors of the trimethoprim-resistant DfrA1 protein through high-throughput computational screening of 3,601 newly synthesized chemical compounds sourced from theChemDivdatabase. We conducted high-throughput computational optimization and screening of a library containing 3,601 compounds against the DfrA1 protein fromK. pneumoniaeandE. colito identify potential drug candidates (DCs). Through this extensive approach, we identified six promising DCs, labeled DC1 to DC6, as potential inhibitors of DfrA1. Each DC demonstrated strong initial binding affinity and favorable chemical interactions with the DfrA1 binding sites when compared to the effective drug Iclaprim (effective antibiotic against DfrA1), used as a control. To validate these findings, we further investigated the molecular mechanisms of inhibition, focusing on the thermodynamic properties of the promising DCs. Furthermore, molecular dynamics simulation (MDS) validated the inhibitory efficacy of these six DCs against the DfrA1 protein. Our results showed that DC4 (an organoflourinated compound) and DC6 (a benzimidazol compound) showed superior efficacy against the DfrA1 protein than the control drug, particularly regarding stability, solvent-accessible surface area, solvent exposure, polarity, and binding site interactions, which influence their residence time and efficacy. Overall, findings of this study suggest that DC4 and DC6 have the potential to act as inhibitors against the DfrA1, offering promising prospects for the treatment and management of infections caused by trimethoprim-resistantK. pneumoniaeandE. coliin both humans and animals.
Pathogen threat proximity shapes host extracellular vesicle production in pre-infection response
Authors: Kołodziejska Klaudia , Szczepańska Agata , Pujol Nathalie , Pokrzywa Wojciech , Turek Michał 
Published: November 2024

AbstractExtracellular vesicles (EVs) play a crucial role in immune responses, yet it remains unclear whether pathogen metabolites alone can stimulate EV production prior to infection. UsingCaenorhabditis elegans, we investigate this question through the lens of exophers – large, evolutionarily conserved EVs known to enhance proteostasis, extend lifespan, and improve reproductive fitness. Our study uncovers distinct regulatory mechanisms driving EV production in response to pathogen-derived volatile and non-volatile metabolites, providing insights into host-pathogen signaling before physical interaction. We reveal a sophisticated network that adjusts EV production based on pathogen proximity: non-volatile metabolites, signaling an immediate threat, activate immune-dependent EV pathways, while volatile metabolites, forewarning potential danger, initiate immunity-independent exopher production. Both responses rely on sensory neurons, with ASK, ADL, and AWC neurons playing central roles in each, and additional input from ASI, AWB, and ASH neurons specifically enhancing non-volatile-induced EV production. Multiple GPCRs, including SRI-19, SRI-36, SRI-39, and SRR-6, are crucial for the non-volatile response, with signal integration mediated by the AIB interneuron and NPR-9 receptor in both responses. Notably, volatile-induced exopher production enhances offspring survival against pathogens but compromises maternal survival. Thus, our study shows thatC. elegansdistinguishes pathogen proximity through metabolite types, activating EV-dependent physiological responses tailored to either immediate or anticipated threats to optimize survival across generations.
Combining metabolic engineering and fermentation optimization to achieve cost-effective oil production byCutaneotrichosporon oleaginosus
Authors: Duman-Özdamar Zeynep Efsun , Veloo Rudolf Marcel , Tsepani Elena , Julsing Mattijs K. , Martins dos Santos Vitor A.P. , Hugenholtz Jeroen , Suarez-Diez Maria 
Published: November 2024

AbstractMicrobial oils, produced by oleaginous microorganisms, offer a sustainable alternative to plant-derived oils. Among these microorganisms,Cutaneotrichosporon oleaginosusattracts attention as a promising microbial cell factory for sustainable oil production due to its capacity to accumulate lipids with a similar composition to palm oil. AlthoughC. oleaginosuscan reach higher lipid contents than other oleaginous yeasts, suboptimal lipid yields and productivity limit economic feasibility. Enhanced productivity is necessary to have a feasible microbial oil production process viaC. oleaginosus. In this study, we followed a combinatorial approach for strain design and bioprocess development to improve the lipid content and lipid yield. Initially, we deployed a full factorial design with genetic factors (ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC), threonine synthase (TS)) and carbon-to-nitrogen ratio (C/N) in the medium. The C/N ratio appeared to have the most impact on oil accumulation. Combined with genetic modifications, lipid content and lipid yield increased by 1.6-fold. In a two-stage fermentation approach at a 2L scale, the triple transformant overexpressingACL,ACC, andTSoutperformed the wild-type by achieving a lipid content of 75.4% (w/w) with lipid productivity of 0.40 g L-1h-1and around 0.30 g lipids/g glycerol. In all, we established a cultivation strategy and strain that reached almost the theoretical maximum yield, and highest lipid content reported for a medium containing glycerol as a carbon source. These results strengthen the basis of usingC. oleaginousas a platform for microbial oil production, thereby facilitating the development of processes substituting palm oil with a sustainable alternative.HighlightsFull factorial design allowed selection of the best performer transformant.Overexpression ofACL1, ACC,andTSinC. oleaginosusprovided higher lipid yield.Two-stage fermentation enhanced the lipid content of wild-type and transformant.Graphical Abstract
Disrupted activation of pain networks during attack imagery in patients with episodic migraine
Authors: Perdigão Alexandre , Esteves Inês , Fouto Ana R , Ruiz-Tagle Amparo , Caetano Gina , Gil-Gouveia Raquel , Figueiredo Patrícia 
Published: November 2024

AbstractMigraine is a prevalent and disabling brain disorder characterized by recurrent headache attacks alternating with pain-free periods. Patients with migraine exhibit altered brain activation in response to experimental nociceptive stimuli compared to healthy controls, suggesting impaired pain inhibition mechanisms. However, the relevance of these alterations to the underlying pathophysiology of migraine attacks remains unclear. To explore this relationship, we propose a novel pain imagery paradigm aimed to induce brain activation patterns associated with migraine attacks specifically during pain-free.The task required patients to alternate between imagining a severe migraine attack and being headache free, while healthy controls imagined severe physical head pain (e.g., toothache) and pain relief. We collected fMRI data from 14 episodic migraine without aura patients in the interictal phase and 15 healthy controls performing this task.Both patients and controls activated pain-related brain areas during imagery of pain relative to pain relief. Moreover, controls also activated the medial pain system associated with pain inhibition and attentional modulation of pain via top-down pathways. In contrast, patients significantly deactivated these areas, namely the anterior cingulate cortex and dorsolateral prefrontal cortex. Collectively, our findings indicate altered functioning of pain networks in migraine patients, suggesting a disease-related dysregulation of pain inhibition. Eventually, the proposed attack imagery paradigm may provide a promising alternative to studies of pain mechanisms in migraine research.
Therapeutic window for treatment of prion disease defined by timed depletion of Prion protein
Authors: Bradford Barry M. , Marshall Alison , Tuzi Nadia L. , Brown Deborah , Kisielewski Dorothy , Summers Kim M. , Perry V. Hugh , Piccardo Pedro , Clarke Alan R. , Manson Jean C. 
Published: November 2024

AbstractThere is no effective treatment preventing the progression of neurodegenerative diseases such as prion and Alzheimer’s diseases. These fatal diseases of the central nervous system, involve progressive accumulation of a misfolded protein long before overt clinical signs of disease. Removal of prion protein early in the pathological process appears to halt the progression however, it is not known whether intervention at later disease stages could be effective. We investigated the potential for intervention throughout the course of prion disease, by developing a mouse model in whichPrnpexpression can be manipulated in a tissue specific and time dependent manner. DepletingPrnpfrom neuronal populations in CNS throughout the preclinical phase substantially prolonged incubation. The pathology was dramatically altered to a pattern of astrocytic associated prion deposition. However once overt clinical symptoms of disease were apparentPrnpdepletion did not alter disease progression. This study establishes a wide window for intervention, and suggests timely treatment could delay the onset of clinical disease potentially well beyond the lifetime of an individual.
High Resolution Spatial Mapping of Microbiome-Host Interactions viain situPolyadenylation and Spatial RNA Sequencing
Authors: Ntekas Ioannis , Takayasu Lena , McKellar David W. , Grodner Benjamin M. , Holdener Chase , Schweitzer Peter , Sauthoff Maya , Shi Qiaojuan , Brito Ilana L. , De Vlaminck Iwijn 
Published: November 2024

ABSTRACTInter-microbial and host–microbial interactions are thought to be critical for the functioning of the gut microbiome, but few tools are available to measure these interactions. Here, we report a method for unbiased spatial sampling of microbiome-host interactions in the gut at one micron resolution. This method combines enzymaticin situpolyadenylation of both bacterial and host RNA with spatial RNA-sequencing. Application of this method in a mouse model of intestinal neoplasia revealed the biogeography of the mouse gut microbiome as function of location in the intestine, frequent strong inter-microbial interactions at short length scales, shaping of local microbiome niches by the host, and tumor-associated changes in the architecture of the host-microbiome interface. This method is compatible with broadly available commercial platforms for spatial RNA-sequencing, and can therefore be readily adopted to broadly study the role of short-range, bidirectional host-microbe interactions in microbiome health and disease.
Dendritic synaptic integration modes underin vivo-like states
Authors: Ceballos Cesar C. , Pena Rodrigo F. O. 
Published: November 2024

AbstractThe neural code remains undiscovered and understanding synaptic input integration underin vivo-like conditions is just the initial step toward unraveling it. Synaptic signals generate fast dendritic spikes through two main modes of temporal summation: coincidence detection and integration. In coincidence detection, dendrites fire only when multiple incoming signals arrive in rapid succession, whereas integration involves summation of postsynaptic potentials over longer periods with minimal membrane leakage. This process is influenced by ionic properties, especially as the membrane potential approaches the firing threshold, where inactivating currents play a critical role. However, the modulation of temporal summation by these currents underin vivo-like conditions has not been thoroughly studied. In our research, we used computer simulations to investigate how three inactivating currents — A-type potassium, T-type calcium, and transient sodium — affect temporal summation. We found that calcium and sodium currents promote integrative behavior in dendrites, while potassium currents enhance their ability to act as coincidence detectors. By adjusting the levels of these currents in dendrites, neurons can flexibly switch between integration and coincidence detection modes, providing them with a versatile mechanism for complex tasks like multiplexing. This flexibility could be key to understanding how neural circuits process information in real time.
Challenges and promises in optimising a non-clinical protocol of intracerebroventricular human neural stem cell transplantation in ALS
Authors: Lombardi Ivan , Ferrero Clelia , Vulcano Edvige , Rasà Daniela Maria , Gelati Maurizio , Campos Diego Pastor , Carletti Rose Mary , de la Morena Silvia , Profico Daniela Celeste , Longobardi Sabrina , Lazzarino Elisa , Perciballi Elisa , Rosati Jessica , Perez Salvador Martinez , Vercelli Alessandro , Boido Marina , Ferrari Daniela 
Published: November 2024

AbstractBackground and aimsNeural stem cell (NSC) transplantation holds promising therapeutic potential for neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). However, pre-clinical studies and early-phase clinical trials have faced challenges hindering the effective clinical translation of this approach. Crucial hurdles include the side-effects of prolonged immunosuppression, concerns regarding cell origin and transplantation dosage, identification of the most appropriate therapeutic window, and invasiveness of surgical procedures. Here, we show challenges and promises in optimizing a non-clinical protocol to assess safety and efficacy of human NSC (hNSC) intracerebroventricular (ICV) transplantation for ALS.MethodsWe evaluated the safety of administering up to 1×106hNSCs in immunodeficient mice and assessed their potential efficacy in reducing ALS hallmarks employing the SOD1G93Amouse model. Both, transient (15 days) and prolonged immunosuppression regimens, at low (15 mg/kg) and high (30 mg/kg) doses, were tested along with two different cell dosages (3×105and 1×106).ResultsBilateral ICV injection of up to 1×106hNSCs proved to be safe, with no evidence of tumor formation. At 40 days post-transplantation, hNSCs induced a trend toward delaying motor decline and reducing spinal cord (SC) microgliosis when transplanted under prolonged high-dose (30 mg/kg) immunosuppression.ConclusionsOur study suggests that: (i) a bilateral ICV transplantation of 1×106hNSCs is safe and non-tumorigenic in immunodeficient hosts; (ii) sustained high-dose immunosuppression is essential for ensuring cell survival in immunocompetent mice; and (iii) hNSC transplantation may provide therapeutic benefits in ALS by delaying motor decline and reducing microgliosis. This study also highlights persisting hurdles that need to be further addressed, such as the aggressive murine immune response to exogenous cells.
Quantitative mapping of cerebrovascular reactivity amplitude and delay with breath-hold BOLD fMRI when end-tidal CO2quality is low
Authors: Clements Rebecca G. , Zvolanek Kristina M. , Reddy Neha A. , Hemmerling Kimberly J. , Bayrak Roza G. , Chang Catie , Bright Molly G. 
Published: November 2024

AbstractCerebrovascular reactivity (CVR), the ability of cerebral blood vessels to dilate or constrict in order to regulate blood flow, is a clinically useful measure of cerebrovascular health. CVR is often measured using a breath-hold task to modulate blood CO2levels during an fMRI scan. Measuring end-tidal CO2(PETCO2) with a nasal cannula during the task allows CVR amplitude to be calculated in standard units (vascular response per unit change in CO2, or %BOLD/mmHg) and CVR delay to be calculated in seconds. The use of standard units allows for normative CVR ranges to be established and for CVR comparisons to be made across subjects and scan sessions. Although breath-holding can be successfully performed by diverse patient populations, obtaining accurate PETCO2measurements requires additional task compliance; specifically, participants must breathe exclusively through their nose and exhale immediately before and after each breath hold. Meeting these requirements is challenging, even in healthy participants, and this has limited the translational potential of breath-hold fMRI for CVR mapping. Previous work has focused on using alternative regressors such as respiration volume per time (RVT), derived from respiratory belt measurements, to map CVR. Because measuring RVT does not require additional task compliance from participants, it is a more feasible measure than PETCO2.However, using RVT does not produce CVR in standard units. In this work, we explored how to achieve CVR maps, in standard units, when breath-hold task PETCO2data quality is low. First, we evaluated whether RVT could be scaled to units of mmHg using a subset of PETCO2data of sufficiently high quality. Second, we explored whether a PETCO2timeseries predicted from RVT using deep learning allows for more accurate CVR measurements. Using a dense-mapping breath-hold fMRI dataset, we showed that both rescaled RVT and rescaled, predicted PETCO2can be used to produce maps of CVR amplitude and delay in standard units with strong absolute agreement to ground-truth maps. However, the rescaled, predicted PETCO2regressor resulted in superior accuracy for both CVR amplitude and delay. In an individual with regions of increased CVR delay due to Moyamoya disease, the predicted PETCO2regressor also provided greater sensitivity to pathology than RVT. Ultimately, this work will increase the clinical applicability of CVR in populations exhibiting decreased task compliance.