bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing Neural Correlates of Memory Encoding and Maintenance for Foveal and Peripheral Stimuli
Authors: Kandemir G. , Olivers C.N.L. 
Published: October 2023

AbstractVisual working memory is believed to rely on top-down attentional mechanisms that sustain active sensory representations in early visual cortex. However, both bottom-up sensory input and top-down attentional modulations thereof have been shown to be biased towards the fovea, at the expense of the periphery, and initially peripheral percepts may even be assimilated by foveal processing. This raises the question whether and how visual working memory differs for central and peripheral input. To address this, we conducted a delayed orientation recall task in which an orientation stimulus was presented either at the center of the screen or at 15° eccentricity to the left or right. Response accuracy, electroencephalographic (EEG) activity and gaze position were recorded from 30 participants. Accuracy was slightly but significantly higher for foveal versus peripheral memories. Orientation decoding analyses of the EEG signals revealed a clear dissociation between early sensory and later maintenance signals. While sensory signals were clearly decodable for the central location, they were not for peripheral locations. In contrast, maintenance signals were decodable to an equal extent for both foveal and peripheral memories, suggesting comparable top-down components regardless of eccentricity. Moreover, while memory representations were initially spatially specific and reflected in voltage fluctuations, later in the maintenance period they generalized across locations, as emerged in alpha oscillations, thus revealing a dynamic transformation within memory. Moreover, these transformed representations remained accessible through sensory impulse-driven perturbations, unveiling the underlying memory state. The eccentricity-driven dissociation between disparate sensory and common maintenance representations indicates that storage activity patterns as measured by EEG reflect signals beyond primary visual cortex.
Divergent evolutionary strategies preempt tissue collision in fly gastrulation
Authors: Dey Bipasha , Kaul Verena , Kale Girish , Scorcelletti Maily , Takeda Michiko , Wang Yu-Chiun , Lemke Steffen 
Published: October 2023

AbstractMetazoan development proceeds through a series of morphogenetic events that sculpt body plans and organ structures. In the early embryonic stages, morphogenetic processes involving growth and deformation occur concurrently. Forces generated in one tissue can thus increase mechanical stress in the neighboring tissue, potentially disrupting spatial patterning, morphological robustness, and consequently decreasing organismal fitness. How organisms evolved mechanisms to reduce or release inter-tissue stresses remains poorly understood. Here we combined phylogenetic survey across a whole insect order (Diptera), quantitative live imaging, and functional mechanical perturbation to investigate the evolution of mechanical stress management during epithelial expansions in the gastrulating fly embryos. We find that two distinct cellular mechanisms exist in Diptera to prevent the accumulation of compressive stress that can arise when the expanding head and trunk tissues collide. In Cyclorrhapha, a monophyletic dipteran subgroup including the fruit flyDrosophila melanogaster, the head-trunk boundary undergoes active out-of-plane deformation to form a transient epithelial fold, called the cephalic furrow (CF), which acts as a mechanical sink to preempt head-trunk collision. Genetic or optogenetic elimination of the CF leads to tissue buckling, yielding deleterious effects of axial distortion that likely results from unmitigated release of compressive stress. Non-cyclorrhaphan flies, by contrast, lack CF formation and instead display widespread out-of-plane division in the head, which shortens the duration of its expansion and reduces surface area increase. Reorienting head mitosis inDrosophilafrom in-plane to out-of-plane partially suppresses the need for epithelial out-of-plane deformation, suggesting that out-of-plane division can act as an alternative mechanical sink to prevent tissue collision. Our data suggest that programs of mechanical stress management can emerge abruptly under selective pressure of inter-tissue mechanical conflict in early embryonic development.
Mapping lung hematopoietic progenitors: Developmental kinetics and response to Influenza A viral infection
Authors: Mincham Kyle T. , Lauzon-Joset Jean-Francois , Read James F. , Holt Patrick G. , Stumbles Philip A. , Strickland Deborah H. 
Published: October 2023

AbstractThe bone marrow is a specialised niche responsible for the maintenance of hematopoietic stem and progenitor cells during homeostasis and inflammation. Recent studies however have extended this essential role to the extramedullary and extravascular lung microenvironment. Here, we provide further evidence for a reservoir of hematopoietic stem and progenitor cells within the lung from embryonic day 18.5 until adulthood. These lung progenitors display distinct microenvironment-specific developmental kinetics compared to their bone marrow counterparts, exemplified by a rapid shift from a common myeloid to megakaryocyte-erythrocyte progenitor dominated niche with increasing age. In adult mice, Influenza A viral infection results in a transient reduction in multipotent progenitors within the lungs, with a parallel increase in downstream granulocyte-macrophage progenitors and dendritic cell populations associated with acute viral infections. Our findings suggest lung hematopoietic progenitors play a role in re-establishing immunological homeostasis in the respiratory mucosa, which may have significant clinical implications for maintaining pulmonary health following inflammatory perturbation.
Menstrual cycle-driven hormone concentrations co-fluctuate with white and grey matter architecture changes across the whole brain
Authors: Rizor Elizabeth J. , Babenko Viktoriya , Dundon Neil M. , Beverly-Aylwin Renee , Stump Alexandra , Hayes Margaret , Herschenfeld-Catalan Luna , Jacobs Emily G. , Grafton Scott T. 
Published: October 2023

AbstractCyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA), while follicle-stimulating hormone (FSH) was directly proportional to cortical thickness. Within several individual regions, FSH and progesterone demonstrated opposing associations with mean diffusivity and cortical thickness. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Lastly, progesterone was associated with increased tissue and decreased CSF volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and cortical thickness coinciding with menstrual cycle-driven hormone rhythms. Strong brain-hormone interaction effects may not be limited to classically known HPG-axis receptor-dense regions.
Parental infertility and offspring cardiometabolic trajectories up to 25 years: a pooled analysis of three European cohorts
Authors: Hernáez Álvaro , Elhakeem Ahmed , Barros Henrique , Vrijkotte Tanja G. M. , Fraser Abigail , Lawlor Deborah A. , Magnus Maria C. 
Published: October 2023

ABSTRACTObjectiveTo assess whether parental infertility is associated with differences in cardiometabolic trajectories in offspring from childhood to 25 years of age.DesignPooled analysis of three European pregnancy cohort studies.SubjectsUp to 14,609 singletons from three pregnancy cohorts (the UK Avon Longitudinal Study of Parents and Children, the Portuguese Geraçao 21, and the Amsterdam Born Children and their Development study).ExposureParental infertility defined as time-to-pregnancy ≥12 months.Main Outcome MeasuresTrajectories of body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose from childhood to 25 years of age were compared in offspring of couples with and without infertility. Trajectories were modelled using mixed-effects models with natural cubic splines adjusting for cohort, sex of the offspring, and maternal factors (age, body mass index, smoking, educational level, parity, and ethnicity). Predicted levels of cardiometabolic traits up to 25 years of age were compared by parental infertility.ResultsOffspring of couples with infertility had increasingly higher BMI (difference in mean predicted levels by age 25: +1.09 kg/m2, 95% confidence interval [0.68 to 1.50]) and suggestively higher DBP at age 25 (+1.21 mmHg [0.00 to 2.43]). Their LDL-C tended to be higher, and their HDL-C values tended to be lower over time (age 25, LDL-C: +4.07% [-0.79 to 8.93]; HDL-C: −2.78% [-6.99 to 1.43]). At middle-late adolescence, offspring of couples with infertility had higher waist circumference (age 17: +1.05 cm [0.11 to 1.99]) and SBP (age 17: +0.93 mmHg [0.044 to 1.81]), but these differences attenuated at later ages. No clear inter-group differences in triglyceride and glucose trajectories were observed. Further adjustment for paternal age, body mass index, smoking, and educational level, and both parent’s history of diabetes and hypertension in the cohort with this information available (Avon Longitudinal Study of Parents and Children) did not attenuate inter-group differences.ConclusionOffspring of couples with infertility have increasingly higher BMI over the years, suggestively higher blood pressure levels, and tend to have greater values of LDL-C and lower values of HDL-C with age.
Modeling Sepsis-Associated ARDS Using a Lung Endothelial Microphysiological System
Authors: Liang Nai-Wen , Wilson Carole , Davis Brooke , Wolf Ian , Qyli Tonela , Moy Joy , Beebe David J. , Schnapp Lynn M. , Kerr Sheena C. , Faust Hilary E. 
Published: October 2023

AbstractAcute respiratory distress syndrome due to non-pulmonary causes exhibits prominent endothelial activation which is challenging to assess in critically ill patients. Preclinicalin vivomodels of sepsis and ARDS have failed to yield useful therapies in humans, perhaps due to interspecies differences in inflammatory responses. Use of microphysiological systems (MPS) offer improved fidelity to human biological responses and better predict pharmacological responses than traditional culture. We adapted a lung endothelial MPS based on the LumeNEXT platform to evaluate the effect of plasma from critically ill sepsis patients on endothelial permeability, adhesion molecule expression and inflammatory cytokine production. Lumens incubated with sepsis plasma exhibited areas of contraction, loss of cellular coverage, and luminal defects. Sepsis plasma-incubated lumens had significantly increased permeability compared to lumens incubated with healthy donor plasma. ICAM-1 expression increased significantly in lumens incubated with sepsis plasma compared with those incubated with healthy control plasma, while concentrations of IL-6, IL-18, and soluble VEGF-R1 increased in sepsis plasma before and after incubation in the MPS compared with healthy control plasma. Use of the lung endothelial MPS may enable interrogation of specific mechanisms of endothelial dysfunction that promote ARDS in sepsis patients.
Cell specific single viral vector CRISPR/Cas9 editing and genetically encoded tool delivery in the central and peripheral nervous systems
Authors: Moffa Jamie C. , Bland India N. , Tooley Jessica R. , Kalyanaraman Vani , Heitmeier Monique , Creed Meaghan C. , Copits Bryan A. 
Published: October 2023

AbstractGene manipulation strategies using germline knockout, conditional knockout, and more recently CRISPR/Cas9 are crucial tools for advancing our understanding of the nervous system. However, traditional gene knockout approaches can be costly and time consuming, may lack cell-type specificity, and can induce germline recombination. Viral gene editing presents and an exciting alternative to more rapidly study genes of unknown function; however, current strategies to also manipulate or visualize edited cells are challenging due to the large size of Cas9 proteins and the limited packaging capacity of adeno-associated viruses (AAVs). To overcome these constraints, we have developed an alternative gene editing strategy using a single AAV vector and mouse lines that express Cre-dependent Cas9 to achieve efficient cell-type specific editing across the nervous system. Expressing Cre-dependent Cas9 in specific cell types in transgenic mouse lines affords more space to package guide RNAs for gene editing together with Cre-dependent, genetically encoded tools to manipulate, map, or monitor neurons using a single virus.We validated this strategy with three commonly used tools in neuroscience: ChRonos, a channelrhodopsin, for manipulating synaptic transmission using optogenetics; GCaMP8f for recording Ca2+ transients using fiber photometry, and mCherry for anatomical tracing of axonal projections. We tested these tools in multiple brain regions and cell types, including GABAergic neurons in the nucleus accumbens (NAc), glutamatergic neurons projecting from the ventral pallidum (VP) to the lateral habenula (LHb), dopaminergic neurons in the ventral tegmental area (VTA), and parvalbumin (PV)-positive proprioceptive neurons in the periphery. This flexible approach should be useful to identify novel genes that affect synaptic transmission, circuit activity, or morphology with a single viral injection.
A conserved ESCRT-II-like protein participates in the biogenesis and maintenance of thylakoid membranes
Authors: Yilmazer Irem , Vetrano Pamela , Eicke Simona , Abt Melanie R. , Traverso Eleonora , Morosinotto Tomas , Zeeman Samuel C. , Ramundo Silvia , Sharma Mayank 
Published: October 2023

AbstractThylakoids are membrane-bound compartments located in cyanobacteria and chloroplasts of plants and algae. They play an indispensable role in the light-driven reactions that enable photosynthetic organisms to convert water and carbon dioxide into oxygen and sugars. The biogenesis and maintenance of thylakoid membranes is a critical yet underappreciated area of research. One of the few known critical regulators of this process, VIPP1 (Vesicle-Inducing Protein in Plastids 1), was recently shown to be structurally similar to ESCRT-III proteins — the first evidence for ESCRT-like (Endosomal Sorting Complex Required for Transport) machinery in chloroplasts. Here, we used an affinity purification approach in two distantly related photosynthetic eukaryotes, the green algaChlamydomonas reinhardtiiand the plantArabidopsis thaliana, to discover proteins that interact with VIPP1. Among several newly identified proteins, we focused on a highly conserved but uncharacterized protein (VIPP1-Associated protein 1, VIA1) that robustly interacts with VIPP1 in both systems. VIA1 is predicted to contain a winged-helix domain, a characteristic feature of ESCRT-II proteins that mediates the interaction with ESCRT-III proteins. The absence of VIA1 causes thylakoid swelling upon exposure to high light in Chlamydomonas and defective thylakoid biogenesis in the newly emerging leaf tissue in Arabidopsis, thereby delaying chloroplast development in this tissue. We propose that VIA1 is part of a previously unrecognized chloroplast ESCRT-like system that plays a critical role in forming, remodeling, and repairing photosynthetic membranes.Significance StatementThylakoid membranes are essential for photosynthesis, yet their biogenesis and maintenance are poorly understood. Of the few known proteins involved in these processes, VIPP1 stands out due to its similarity to ESCRT-III, an integral component of the ESCRT machinery that is responsible for membrane remodeling and trafficking in the cytoplasm of eukaryotes. Here we report the discovery of VIA1, a conserved protein that interacts with VIPP1 and participates in thylakoid biogenesis and remodeling in two distantly related photosynthetic organisms. Because VIA1 contains a predicted winged-helix domain, a hallmark feature of ESCRT-II proteins that mediates the interaction with ESCRT-III proteins, our data support the hypothesis that universal, mechanistic principles govern membrane remodeling across all living organisms.
Virus-host protein co-expression networks reveal temporal organization and strategies of viral infection
Authors: Aguirre Jacobo , Guantes Raúl 
Published: October 2023

ABSTRACTViral replication is a complex dynamical process involving the global remodelling of the host cellular machinery across several stages. In this study, we provide a unified view of the virus-host interaction at the proteome level reconstructing protein co-expression networks from quantitative temporal data of four large DNA viruses. We take advantage of a formal framework, the theory of interacting networks, to describe the viral infection as a dynamical system taking place on a network of networks where perturbations induced by viral proteins spread to hijack the host proteome for the virus benefit. Our methodology demonstrates how the viral replication cycle can be effectively examined as a complex interaction between protein networks, providing useful insights into the viral and host’s temporal organization and strategies, key protein nodes targeted by the virus and dynamical bottlenecks during the course of the infection.
Lactoylglutathione promotes inflammatory signaling in macrophages
Authors: Trujillo Marissa N. , Jennings Erin Q. , Hoffman Emely A. , Zhang Hao , Phoebe Aiden M. , Mastin Grace E. , Kitamura Naoya , Reisz Julie A , Megill Emily , Kantner Daniel , Marcinkiewicz Mariola M. , Twardy Shannon M. , Lebario Felicidad , Chapman Eli , McCullough Rebecca L. , D’Alessandro Angelo , Snyder Nathaniel W. , Cusanovich Darren A. , Galligan James J. 
Published: October 2023

AbstractChronic, systemic inflammation is a pathophysiological manifestation of metabolic disorders. Inflammatory signaling leads to elevated glycolytic flux and a metabolic shift towards aerobic glycolysis and lactate generation. This rise in lactate corresponds with increased generation of lactoylLys modifications on histones, mediating transcriptional responses to inflammatory stimuli. Lactoylation is also generated through a non-enzymatic S-to-N acyltransfer from the glyoxalase cycle intermediate, lactoylglutathione (LGSH). Here, we report a regulatory role for LGSH in inflammatory signaling. In the absence of the primary LGSH hydrolase, glyoxalase 2 (GLO2), RAW264.7 macrophages display significant elevations in LGSH, while demonstrating a potentiated inflammatory response when exposed to lipopolysaccharides, corresponding with a rise in histone lactoylation. Interestingly, our data demonstrate that lactoylation is associated with more compacted chromatin than acetylation in an unstimulated state, however, upon stimulation, regions of the genome associated with lactoylation become markedly more accessible. Lastly, we demonstrate a spontaneous S-to-S acyltransfer of lactate from LGSH to CoA, yielding lactoyl-CoA. This represents the first known mechanism for the generation of this metabolite. Collectively, these data suggest that LGSH, and not intracellular lactate, is a primary contributing factor facilitating the inflammatory response.
Circulating senescent myeloid cells drive blood brain barrier breakdown and neurodegeneration
Authors: Wilk C. Matthias , Cathomas Flurin , Török Orsolya , Le Berichel Jessica , Park Matthew D. , Heaton George R. , Hamon Pauline , Troncoso Leanna , Scull Brooks P. , Dangoor Diana , Silvin Aymeric , Fleischmann Ryan , Belabed Meriem , Lin Howard , Taouli Elias Merad , Boettcher Steffen , Manz Markus G. , Kofler Julia K. , Yue Zhenyu , Lira Sergio A. , Ginhoux Florent , Crary John F. , McClain Kenneth L. , Picarsic Jennifer L. , Russo Scott J. , Allen Carl E. , Merad Miriam 
Published: October 2023

SummaryNeurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis (LCH) is an inflammatory neoplastic disorder caused by hematopoietic progenitors expressing MAPK activating mutations that differentiate into senescent myeloid cells that drive lesion formation. Some patients with LCH subsequently develop progressive and incurable neurodegeneration (LCH-ND). Here, we show that LCH-ND is caused by myeloid cells that are clonal with peripheral LCH cells. We discovered that circulatingBRAFV600E+myeloid cells cause the breakdown of the blood-brain barrier (BBB), enhancing migration into the brain parenchyma where they differentiate into senescent, inflammatory CD11a+macrophages that accumulate in the brainstem and cerebellum. Blocking MAPK activity and senescence programs reduced parenchymal infiltration, neuroinflammation, neuronal damage and improved neurological outcome in preclinical LCH-ND. MAPK activation and senescence programs in circulating myeloid cells represent novel and targetable mechanisms of ND.
Using encrypted genotypes and phenotypes for collaborative genomic analyses to maintain data confidentiality
Authors: Zhao Tianjing , Wang Fangyi , Mott Richard , Dekkers Jack , Cheng Hao 
Published: October 2023

ABSTRACTTo adhere to and capitalize on the benefits of the FAIR (Findable, Accessible, Interoperable and Reusable) principles in agricultural genome-to-phenome studies, it is crucial to address privacy and intellectual property issues that prevent sharing and reuse of data in research and industry. Direct sharing of genotype and phenotype data is often prohibited due to intellectual property and privacy concerns. Thus there is a pressing need for encryption methods that obscure confidential aspects of the data, without affecting the outcomes of certain statistical analyses. A homomorphic encryption method for genotypes and phenotypes (HEGP) has been proposed for single-marker regression in genome-wide association studies using linear mixed models with Gaussian errors. This methodology permits frequentist likelihood-based parameter estimation and inference. In this paper, we extend HEGP to broader applications in genome-to-phenome analyses. We show that HEGP is suited to commonly used linear mixed models for genetic analyses of quantitative traits including GBLUP and RR-BLUP, as well as Bayesian variable selection methods (e.g., those in Bayesian Alphabet), for genetic parameter estimation, genomic prediction, and genome-wide association studies. By advancing the capabilities of HEGP, we offer researchers and industry professionals a secure and efficient approach for collaborative genomic analyses while preserving data confidentiality.