bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketogenic diet prevents sucrose withdrawal-induced anxiety-like behaviour in male mice
Authors: Kumar Mohit , Lal Roshan , Bhatt Babita , Bishnoi Mahendra 
Published: March 2023

AbstractSugar bingeing has been shown to induce withdrawal effects when sugar is no longer available in the diet. In this study, we investigated the sex differences in sugar-addiction-like behaviour and the effects of the ketogenic diet on these outcomes. We used the two-bottle sucrose choice paradigm as a pre-clinical sucrose overeating and withdrawal model. Female mice consumed more sucrose than males when given free access to water and 10% sucrose for four weeks. One week of sucrose withdrawal after four weeks of consecutive sucrose overeating showed anxiety-like behaviour in male mice. However, the ketogenic diet did not affect sucrose overconsumption in males and females but prevented the sucrose withdrawal-induced anxiety-like behaviour in male mice with a concomitant increase incFosmRNA in the prefrontal cortex. These findings provide evidence of sex differences in sucrose addiction-like behaviour and also indicate that a ketogenic diet may prevent sucrose withdrawal-induced anxiety-like behaviour in males. However, further research is needed to explore the underlying molecular mechanisms driving sex differences in sugar-addiction-like behaviour and the anxiolytic effects of the ketogenic diet.
Uptake of environmental DNA inBacillus subtilisoccurs all over the cell surface through a dynamic pilus structure
Authors: Kilb Alexandra , Burghard-Schrod Marie , Holtrup Sven , Graumann Peter L. 
Published: March 2023

AbstractAt the transition to stationary phase, a subpopulation ofBacillus subtiliscells can enter the developmental state of competence, where DNA is taken up through the cell envelope, is processed to single stranded DNA, which is incorporated into the genome if sufficient homology between sequences exists. We show here that the initial step of transport across the cell wall occurs via a true pilus structure, with an average length of about 500 nm, which assembles at various places on the cell surface. Once assembled, the pilus remains at one position and can be retracted in a time frame of seconds. The major pilin, ComGC, was studied at a single molecule level in live cells. ComGC was found in two distinct populations, one that would correspond to ComGC freely diffusing throughout the cell membrane, and one that is relatively stationary, likely reflecting pilus-incorporated molecules. The ratio of 65% diffusing and 35% stationary ComGC changed towards more stationary molecules upon addition of external DNA, while the number of pili in the population did not strongly increase. These findings suggest that the pilus assembles stochastically, but engages more pilin monomers from the membrane fraction in the presence of transport substrate. Our data reveal that localized transport of DNA into the cytosol at a single cell pole is preceded by localization throughout the periplasm and efficient uptake through the entire cell surface by a dynamic pilus.ImportanceHorizontal gene transfer (HGT) is important for bacterial evolution and the adaption to new environments. Through HGT, genes can be transferred between bacteria, which can lead to antibiotic resistance development, especially critical with regards to pathogenic bacterial species. One mechanism of HGT is natural competence, through which bacteria can take up DNA under natural conditions and incorporate it into their chromosomes. For DNA uptake, a complex will be formed that is conserved among Gram-positive and Gram-negative bacteria, in spite of different envelope architectures. We show that inBacillus subtilis, where the part of the uptake complex spanning the cell membrane localizes to a single cell pole, transport through the cell wall is mediated by a visible pilus structure that can extend and retract to pull DNA into the periplasm. Thus, DNA uptake from the environment is not limited to polar sites, but is channelled into the cytosol at the pole. Single molecule dynamics of ComGC revealed a static, likely pilus-bound, and a mobile fraction of ComGC within the cell membrane. Addition of environmental DNA increased the static fraction of molecules, showing that pilus dynamics respond to DNA binding.
Mitochondrial morphology dynamics and ROS regulate apical polarity and differentiation inDrosophilafollicle cells
Authors: Uttekar Bhavin , Tomer Darshika , Rikhy Richa 
Published: March 2023

AbstractMitochondrial morphology dynamics regulate signaling pathways during epithelial cell formation and differentiation. The mitochondrial fission protein Drp1 affects the appropriate activation of EGFR and Notch signaling-driven differentiation of posterior follicle cells inDrosophilaoogenesis. The mechanisms by which Drp1 regulates epithelial polarity during differentiation are not known. In this study, we show that Drp1 depleted follicle cells are constricted in early stages and present in multiple layers at later stages with decreased levels of apical polarity protein aPKC. This defect is suppressed by additional depletion of mitochondrial fusion protein Opa1. Opa1 depletion leads to mitochondrial fragmentation and increased reactive oxygen species (ROS) in follicle cells. We find that increasing ROS by depleting the ROS scavengers, mitochondrial SOD2, and catalase also leads to mitochondrial fragmentation. Further, the loss of Opa1, SOD2, and catalase partially restores the defects in epithelial polarity and aPKC along with EGFR and Notch signaling in Drp1 depleted follicle cells. Our results show a crucial interaction between mitochondrial morphology, ROS generation, and epithelial cell polarity formation during the differentiation of follicle epithelial cells inDrosophilaoogenesis.Summary statementMitochondrial fission protein Drp1 regulates epithelial follicle cell differentiation inDrosophilaoogenesis. Increasing ROS and mitochondrial fragmentation suppresses the defects in epithelial polarity, and differentiation in Drp1 depleted follicle cells.
YAP signaling regulates the cellular uptake and therapeutic effect of nanoparticles
Authors: Cassani Marco , Fernandes Soraia , Oliver-De La Cruz Jorge , Durikova Helena , Vrbsky Jan , Patočka Marek , Hegrova Veronika , Klimovic Simon , Pribyl Jan , Debellis Doriana , Skladal Petr , Cavalieri Francesca , Caruso Frank , Forte Giancarlo 
Published: March 2023

AbstractInteractions between living cells and nanoparticles have been extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness and surface charge have been regarded as the main features able to control the fate of cell-nanoparticle interactions. However, the clinical translation of nanotherapies has so far been limited, and there is a need to better understand the biology of cell-nanoparticle interactions. This study investigated the role of cellular mechanosensitive components in cell-nanoparticle interactions. We demonstrate that the genetic and pharmacologic inhibition of yes-associated protein (YAP), a key component of cancer cell mechanosensing apparatus and Hippo pathway effector, improves nanoparticle internalization in triple-negative breast cancer cells regardless of nanoparticle properties or substrate characteristics. This process occurs through YAP-dependent regulation of endocytic pathways, cell mechanics, and membrane organization. Hence, we propose targeting YAP may sensitize triple negative breast cancer cells to chemotherapy and increase the selectivity of nanotherapy.
Olfactory search with finite-state controllers
Authors: Verano Kyrell Vann , Panizon Emanuele , Celani Antonio 
Published: March 2023

AbstractLong-range olfactory search is an extremely difficult task in view of the sparsity of odor signals that are available to the searcher and the complex encoding of the information about the source location. Current algorithmic approaches typically require a continuous memory space, sometimes of large dimensionality, which may hamper their optimization and often obscure their interpretation. Here, we show how finite-state controllers with a small set of discrete memory states are expressive enough to display rich, time-extended behavioral modules that resemble the ones observed in living organisms. Finite-state controllers optimized for olfactory search have an immediate interpretation in terms of approximate clocks and coarse-grained spatial maps, suggesting connections with neural models of search behavior.
Cell Type-specific Hypothalamic Pathways to Brainstem Drive Context-dependent Strategies in Response to Stressors
Authors: Ahmadlou Mehran , Giannouli Maria , van Vierbergen Jacqueline F. M. , van Leeuwen Tom , Bloem Wouter , Houba Janou H. W. , Yasamin Shirazi Maryam , Cazemier J. Leonie , Haak Robin , Dubey Mohit , de Winter Fred , Heimel J. Alexander 
Published: March 2023

SUMMARYAdaptive behavioral responses to stressors are critical for survival. However, which brain areas orchestrate switching the appropriate stress responses to distinct contexts is an open question. This study aimed to identify the cell type-specific brain circuitry governing the selection of distinct behavioral strategies in response to stressors. Through novel mouse behavior paradigms, we observed distinct stressor-evoked behaviors in two psycho-spatially distinct contexts, characterized by stressors inside or outside the safe zone. The identification of brain regions activated in both conditions revealed the involvement of the dorsomedial hypothalamus (DMH). Further investigation using optogenetics, chemogenetics, and photometry uncovered that glutamatergic projections from the DMH to periaqueductal gray (PAG) mediated responses to inside-stressors, while GABAergic projections, particularly from tachykinin1-expressing neurons, played a crucial role in coping with outside-stressors. These findings elucidate the role of cell type-specific circuitry from the DMH to the PAG in shaping behavioral strategies in response to stressors. These findings have the potential to advance our understanding of fundamental neurobiological processes and inform the development of novel approaches for managing context-dependent and anxiety-associated pathological conditions such as agoraphobia and claustrophobia.
VirRep: accurate identification of viral genomes from human gut metagenomic data via a hybrid language representation learning framework
Authors: Dong Yanqi , Chen Wei-Hua , Zhao Xing-Ming 
Published: March 2023

AbstractAccurate identification of viral genomes from metagenomic data provides a broad avenue for studying viruses in the human gut. Here, we introduce VirRep, a novel virus identification method based on a hybrid language representation learning framework. VirRep employs a context-aware encoder and a composition-focused encoder to incorporate the learned knowledge and known biological insights to better describe the source of a DNA sequence. We benchmarked VirRep on multiple human gut virome datasets under different conditions and demonstrated significant superiority than state-of-the-art methods and even combinations of them. A comprehensive validation has also been conducted on real human gut metagenomes to show the great utility of VirRep in identifying high-quality viral genomes that are missed by other methods.
Perinatal Opioid Exposure Leads to Decreased Social Play in Adolescent Male and Female Rats: Potential Role of Oxytocin Signaling in Brain Regions Associated with Social Reward
Authors: Harder Hannah J. , Searles Christopher T. , Vogt Meghan E. , Murphy Anne Z. 
Published: March 2023

AbstractOver the last two decades, the number of infants exposed to opioidsin uterohas quadrupled in the United States, with some states reporting rates as high as 55 infants per 1000 births. Clinical studies report that children previously exposed to opioids during gestation show significant deficits in social behavior, including an inability to form friendships or other social relationships. To date, the neural mechanisms whereby developmental opioid exposure disrupts social behavior remain unknown. Using a novel paradigm of perinatal opioid administration, we tested the hypothesis that chronic opioid exposure during critical developmental periods would disrupt juvenile play. As oxytocin is a major regulator of sociability, the impact of perinatal morphine exposure on oxytocin peptide and receptor expression was also examined. Juvenile play was assessed in vehicle- or morphine-exposed male and female rats at P25, P35, and P45. Classical features of juvenile play were measured, including time spent engaged in social play, time not in contact, number of pins, and number of nape attacks. We report that morphine-exposed females spend less time engaged in play behavior than control males and females, with a corresponding increase in time spent alone. Morphine-exposed females also initiated fewer pins and nape attacks. Oxytocin receptor binding was reduced in morphine-exposed females in the nucleus accumbens, a brain region critical for social reward. Together, these data suggest that females exposed to morphine during critical developmental periods are less motivated to participate in social play, potentially due to alterations in oxytocin-mediated reward signaling.
A computational framework for characterizing normative development of structural brain connectivity in the perinatal stage
Authors: Wu Yihan , Gholipour Ali , Vasung Lana , Karimi Davood 
Published: March 2023

AbstractQuantitative assessment of the brain’s structural connectivity in the perinatal stage is useful for studying normal and abnormal neurodevelopment. However, estimation of the structural connectome from diffusion MRI data involves a series of complex and ill-posed computations. For the perinatal period, this analysis is further challenged by the rapid brain development and difficulties of imaging subjects at this stage. These factors, along with high inter-subject variability, have made it difficult to chart the normative development of the structural connectome. Hence, there is a lack of baseline trends in connectivity metrics that can be used as reliable references for assessing normal and abnormal brain development at this critical stage. In this paper we propose a computational framework, based on spatio-temporal atlases, for determining such baselines. We apply the framework on data from 169 subjects between 33 and 45 postmenstrual weeks. We show that this framework can unveil clear and strong trends in the development of structural connectivity in the perinatal stage. Some of our interesting findings include that connection weighting based on neurite density produces more consistent trends and that the trends in global efficiency, local efficiency, and characteristic path length are more consistent than in other metrics.
A Novel ARNT-Dependent HIF-2α Signaling as a Protective Mechanism for Cardiac Microvascular Barrier Integrity and Heart Function Post-Myocardial Infarction
Authors: Ullah Karim , Ai Lizhuo , Li Yan , Liu Lifeng , Zhang Qin , Pan Kaichao , Humayun Zainab , Piao Lin , Sitikov Albert , Su Qiaozhu , Zhao Qiong , Sharp Willard , Fang Yun , Wu David , Liao James K. , Wu Rongxue 
Published: March 2023

ABSTRACTMyocardial infarction (MI) significantly compromises the integrity of the cardiac microvascular endothelial barrier, leading to enhanced leakage and inflammation that contribute to the progression of heart failure. While HIF2α is highly expressed in cardiac endothelial cells (ECs) under hypoxic conditions, its role in regulating microvascular endothelial barrier function during MI is not well understood. In this study, we utilized mice with a cardiac-specific deletion of HIF2α, generated through an inducible Cre (Cdh5Cre-ERT2) recombinase system. These mice exhibited no apparent phenotype under normal conditions. However, following left anterior descending (LAD) artery ligation-induced MI, they showed increased mortality associated with enhanced cardiac vascular leakage, inflammation, worsened cardiac function, and exacerbated heart remodeling. These outcomes suggest a protective role for endothelial HIF2α in response to cardiac ischemia. Parallel investigations in human cardiac microvascular endothelial cells (CMVECs) revealed that loss of ecHif2α led to diminished endothelial barrier function, characterized by reduced tight-junction protein levels and increased cell death, along with elevated expression of IL6 and other inflammatory markers. These effects were substantially reversed by overexpressing ARNT, a critical dimerization partner for HIF2α during hypoxia. Additionally, ARNT deletion also led to increased CMVEC permeability. Interestingly, ARNT, rather than HIF2α itself, directly binds to the IL6 promoter to suppress IL6 expression. Our findings demonstrate the critical role of endothelial HIF2α in response to MI and identify the HIF2α/ARNT axis as a transcriptional repressor, offering novel insights for developing therapeutic strategies against heart failure following MI.
Cortical thickness and sub-cortical volumes in post-H1N1 narcolepsy type 1: A brain-wide MRI case-control study
Authors: Juvodden Hilde T. , Alnæs Dag , Agartz Ingrid , Andreassen Ole A. , Server Andres , Thorsby Per M. , Westlye Lars T. , Knudsen-Heier Stine 
Published: March 2023

AbstractObjectiveThere was an increased incidence of Narcolepsy type 1(NT1) after the H1N1-mass vaccination in 2009/2010 which has been associated with the Pandemrix®-vaccine. We performed the first case-control comparison of MRI-based global and sub-cortical volume and cortical thickness in post-H1N1(largely Pandemrix®-vaccinated) NT1 patients compared with healthy controls.MethodsWe included 54 post-H1N1 NT1 patients (51 with confirmed hypocretin-deficiency; 48 H1N1-vaccinated with Pandemrix®; 39 females, mean age 21.8 ± 11.0 years) and 114 healthy controls (77 females, mean age 23.2 ± 9.0 years). 3T MRI brain scans were obtained, and the T1-weighted MRI data were processed using FreeSurfer. Group differences among three global and 10 sub-cortical volume measures and 34 cortical thickness measures for bilateral brain regions were tested using general linear models with permutation testing. We corrected for multiple testing with the Benjamini-Hochberg procedure with the false discovery rate at 5%.ResultsPatients had significantly thinner brain cortex bilaterally in the temporal poles (Cohen’s d=0.68,p=0.00080), entorhinal cortex (d=0.60,p=0.0018) and superior temporal gyrus (d=0.60,p=0.0020) compared to healthy controls. The analysis revealed no significant group differences for sub-cortical volumes.ConclusionsPost-H1N1(largely Pandemrix®-vaccinated) NT1 patients have significantly thinner cortex in temporal brain regions compared to controls. We speculate that this effect can be partly attributed to the hypothalamic neuronal change in NT1, including loss of function of the widely projecting hypocretin-producing neurons and secondary effects of the abnormal sleep-wake pattern in NT1. Alternatively, the findings could be specific for post-H1N1 (largely Pandemrix®-vaccinated) NT1 patients.
In silicoagent-based modeling approach to characterize multiplein vitrotuberculosis infection models
Authors: Petrucciani Alexa , Hoerter Alexis , Kotze Leigh , Plessis Nelita Du , Pienaar Elsje 
Published: March 2023

AbstractIn vitromodels ofMycobacterium tuberculosis (Mtb)infection are a valuable tool to examine host-pathogen interactions and screen drugs. With the development of more complexin vitromodels, there is a need for tools to help analyze and integrate data from these models. We introduce an agent-based model (ABM) representation of the interactions between immune cells and bacteria in anin vitrosetting. Thisin silicomodel was used to independently simulate both traditional and spheroid cell culture models by changing the movement rules and initial spatial layout of the cells. These two setups were calibrated to published experimental data in a paired manner, by using the same parameters in both simulations. Within the calibrated set, heterogeneous outputs are seen for outputs of interest including bacterial count and T cell infiltration into the macrophage core of the spheroid. The simulations are also able to predict many outputs with high time resolution, including spatial structure. The structure of a single spheroid can be followed across the time course of the simulation, allowing the relationship between cell localization and immune activation to be explored. Uncertainty analyses are performed for both model setups using latin hypercube sampling and partial rank correlation coefficients to allow for easier comparison, which can provide insight into ideal use cases for the independent setups. Future model iterations can be guided by the limitations of the current model, specifically which parts of the output space were harder to reach. This ABM can be used to represent morein vitro Mtbinfection models due to its flexible structure, providing a powerful analysis tool that can be used in tandem with experiments.Author SummaryTuberculosis is an infectious disease that causes over 1.4 million deaths every year. During infection, immune cells surround the bacteria forming structures called granulomas in the lungs. New laboratory models generate spheroids that aim to recreate these structures to help understand infection and find new ways to treat tuberculosis. Computational modeling is used to compare these newer spheroid models to traditional models, which don’t recreate the structure of the cell clusters. After calibration to data from laboratory experiments to ensure that the computational model can represent both systems, the structures were characterized over time. The traditional and spheroid model were also compared by looking at how model inputs impact outputs, allowing users to figure out when one model should be used over the other. This computational tool can be used to help integrate data from different laboratory models, generate hypothesis to be tested in laboratory models, and predict pathways to be targeted by drugs.
Voltage-dependent volume regulation controls epithelial cell extrusion and morphology
Authors: Mitchell Saranne J. , Pardo-Pastor Carlos , Zangle Thomas A. , Rosenblatt Jody 
Published: March 2023

ABSTRACTEpithelial cells work collectively to provide a protective barrier, yet also turn over rapidly by cell death and division. If the number of dying cells does not match those dividing, the barrier would vanish, or tumors can form. Mechanical forces and thestretch-activated ionchannel (SAC) Piezo1 link both processes; stretch promotes cell division and crowding triggers cell death by initiating live cell extrusion1,2. However, it was not clear how particular cells within a crowded region are selected for extrusion. Here, we show that individual cells transiently shrink via water loss before they extrude. Artificially inducing cell shrinkage by increasing extracellular osmolarity is sufficient to induce cell extrusion. Pre-extrusion cell shrinkage requires the voltage-gated potassium channels Kv1.1 and Kv1.2 and the chloride channel SWELL1, upstream of Piezo1. Activation of these voltage-gated channels requires the mechano-sensitive Epithelial Sodium Channel, ENaC, acting as the earliest crowd-sensing step. Imaging with a voltage dye indicated that epithelial cells lose membrane potential as they become crowded and smaller, yet those selected for extrusion are markedly more depolarized than their neighbours. Loss of any of these channels in crowded conditions causes epithelial buckling, highlighting an important role for voltage and water regulation in controlling epithelial shape as well as extrusion. Thus, ENaC causes cells with similar membrane potentials to slowly shrink with compression but those with reduced membrane potentials to be eliminated by extrusion, suggesting a chief driver of cell death stems from insufficient energy to maintain cell membrane potential.