bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resting-state EEG signatures of Alzheimer’s disease are driven by periodic but not aperiodic changes
Authors: Kopčanová Martina , Tait Luke , Donoghue Thomas , Stothart George , Smith Laura , Flores Sandoval Aimee Arely , Davila-Perez Paula , Buss Stephanie , Shafi Mouhsin M. , Pascual-Leone Alvaro , Fried Peter J. , Benwell Christopher S.Y. 
Published: June 2023

AbstractElectroencephalography (EEG) has shown potential for identifying early-stage biomarkers of neurocognitive dysfunction associated with dementia due to Alzheimer’s disease (AD). A large body of evidence shows that, compared to healthy controls (HC), AD is associated with power increases in lower EEG frequencies (delta and theta) and decreases in higher frequencies (alpha and beta), together with slowing of the peak alpha frequency. However, the pathophysiological processes underlying these changes remain unclear. For instance, recent studies have shown that apparent shifts in EEG power from high to low frequencies can be driven either by frequency specific periodic power changes or rather by non-oscillatory (aperiodic) changes in the underlying 1/f slope of the power spectrum. Hence, to clarify the mechanism(s) underlying the EEG alterations associated with AD, it is necessary to account for both periodic and aperiodic characteristics of the EEG signal. Across two independent datasets, we examined whether resting-state EEG changes linked to AD reflect true oscillatory (periodic) changes, changes in the aperiodic (non-oscillatory) signal, or a combination of both. We found strong evidence that the alterations are purely periodic in nature, with decreases in oscillatory power at alpha and beta frequencies (AD < HC) leading to lower (alpha + beta) / (delta + theta) power ratios in AD. Aperiodic EEG features did not differ between AD and HC. By replicating the findings in two cohorts, we provide robust evidence for purely oscillatory pathophysiology in AD and against aperiodic EEG changes. We therefore clarify the alterations underlying the neural dynamics in AD and emphasise the robustness of oscillatory AD signatures, which may further be used as potential prognostic or interventional targets in future clinical investigations.
Comparing kinetic proofreading and kinetic segregation for T cell receptor activation
Authors: Moffett Alexander S. , Ganzinger Kristina A. , Eckford Andrew W. 
Published: June 2023

AbstractThe T cell receptor (TCR) is a key component of the adaptive immune system, recognizing foreign antigens and triggering an immune response. Competing models exist to explain the high sensitivity and selectivity of the TCR in discriminating ‘self’ from ‘non-self’ antigens, particularly models using kinetic proofreading (KP), kinetic segregation (KS), and combinations of the two. In this paper, we consider the role and importance of KS in TCR activation, using two models: classic KP (cKP), without KS, where antigen-TCR binding is required for activation, and a combination of KP and KS (KS-KP), where only residence within a close contact is required for activation. Building on previous work, our computational model is the first to permit a head-to-head comparison of these modelsin silico. While we find that both models can be used to explain the probability of TCR activation across much of the parameter space, we find biologically important regions in the parameter space where significant differences in performance can be expected. Furthermore, we show that the available experimental evidence may favour the KS-KP model over cKP. Our results may be used to motivate and guide future experiments to determine highly accurate computational models for the TCR.Author summaryThe T cell receptor (TCR) is a master of reliable sensing: it detects faint ‘signals’ (rare ligands derived from foreign proteins) over high ‘noise’ (abundant ligands derived from the body’s own proteins) to set T cells on a course to exterminate pathogens and tumours, a process that is central to our immune response. Despite decades of studying TCR signalling, we still do not know how the TCR can be so exceptionally sensitive and accurate. It is widely believed that kinetic proofreading (KP), in which the TCR binds to an antigen and triggers a series of phosphorylation steps prior to activation, plays an important role. However, recent results suggest that kinetic segregation (KS), in which binding is not required, is also important. These models are mutually exclusive, and yet both appear to explain various aspects of T cell activation.Our work directly addresses this puzzle. We develop a computational modeling framework which can simulate TCR activation by both KP-based and KS-based models, making it possible to compare themin silicofor the first time. Using this framework, we find conditions under which the two models provide different responses, and we show that the limited experimental evidence to date is consistent with KS, which should motivate further investigation.
Developmental transcriptional control of mitochondrial homeostasis is required for activity-dependent synaptic connectivity
Authors: Mohylyak Iryna , Bengochea Mercedes , Pascual-Caro Carlos , Asfogo Noemi , Fonseca-Topp Sara , Danda Natasha , Atak Zeynep Kalender , De Waegeneer Maxime , Plaçais Pierre-Yves , Preat Thomas , Aerts Stein , Corti Olga , de Juan-Sanz Jaime , Hassan Bassem A. 
Published: June 2023

AbstractDuring neuronal circuit formation, local control of axonal organelles ensures proper synaptic connectivity. Whether this process is genetically encoded is unclear and if so, its developmental regulatory mechanisms remain to be identified. We hypothesized that developmental transcription factors regulate critical parameters of organelle homeostasis that contribute to circuit wiring. We combined cell type-specific transcriptomics with a genetic screen to discover such factors. We identified Telomeric Zinc finger-Associated Protein (TZAP) as a temporal developmental regulator of neuronal mitochondrial homeostasis genes, includingPink1. InDrosophila, loss ofdTzapfunction during visual circuit development leads to loss of activity-dependent synaptic connectivity, that can be rescued byPink1expression. At the cellular level, loss ofdTzap/TZAPleads to defects in mitochondrial morphology, attenuated calcium uptake and reduced synaptic vesicle release in fly and mammalian neurons. Our findings highlight developmental transcriptional regulation of mitochondrial homeostasis as a key factor in activity-dependent synaptic connectivity.
Evolution of the gene regulatory network of body axis by enhancer hijacking in amphioxus
Authors: Shi Chenggang , Chen Shuang , Liu Huimin , Li Shiqi , Wang Yanhui , Pan Rongrong , Wu Xiaotong , Li Xuewen , Li Jingjing , Xing Chaofan , Liu Xian , Wang Yiquan , Qu Qingming , Li Guang 
Published: June 2023

AbstractA central goal of evolutionary developmental biology is to decipher the evolutionary pattern of gene regulatory networks (GRNs) that control morphogenesis during embryonic development, and the underlying molecular mechanism of the GRNs evolution. The Nodal signaling that governs the body axes of deuterostomes exhibits a conserved GRN orchestrated principally by Nodal, Gdf1/3 and Lefty. Despite that the GRN retains a conserved function in deuterostomes, the expression patterns ofGdf1/3andNodalare derived in cephalochordate amphioxus, implying a specific rewiring of the GRN in this lineage. Here we examined the regulatory mechanism and evolution of this GRN in amphioxus by functional genetic manipulations. We found that while the amphioxusGdf1/3orthologue shows nearly no expression during embryogenesis, its duplicateGdf1/3-likelinking toLeftyis zygotically expressed in a similar pattern asLefty. Mutant and transgenic analyses revealed thatGdf1/3is no longer crucial for amphioxus axial development. Instead,Gdf1/3-likeassumes this responsibility, likely through hijackingLeftyenhancers. We also showed that amphioxus Nodal has become an indispensable maternal factor to compensate for the loss of maternalGdf1/3expression. We therefore demonstrated a case that the evolution of an ancestral GRN could be triggered by enhancer hijacking events. This pivotal event has allowed the emergence of a new GRN in the extant amphioxus, presumably evolving through a stepwise process. The co-expression ofGdf1/3-likeandLeftyachieved by shared regulatory region may have provided developmental robustness during body axis formation in extant amphioxus, which provides a selection-based hypothesis for the phenomena called developmental system drift.
Using a Riemannian elastic metric for statistical analysis of tumor cell shape heterogeneity
Authors: Li Wanxin , Prasad Ashok , Miolane Nina , Duc Khanh Dao 
Published: June 2023

AbstractWe examine how a specific instance of the elastic metric, the Square Root Velocity (SRV) metric, can be used to study and compare cellular morphologies from the contours they form on planar surfaces. We process a dataset of images from osteocarcoma (bone cancer) cells that includes different treatments known to affect the cell morphology, and perform a comparative statistical analysis between the linear and SRV metrics. Our study indicates superior performance of the SRV at capturing the cell shape heterogeneity, with a better separation between different cell groups when comparing their distance to their mean shape, as well as a better low dimensional representation when comparing stress statistics. Therefore, our study suggests the use of a Riemannian metric, such as the SRV as a potential tool to enhance morphological discrimination for large datasets of cancer cell images.
Pharmacological or genetic inhibition ofScn9aprotects beta-cells while reducing insulin secretion in type 1 diabetes
Authors: Overby Peter , Provenzano Sophia , Nahirney Natalie S. , Dai Xiao-Qing , Sun WenQing Grace , Xia Yi Han , Zhang Jiashuo Aaron , Cen Haoning , Skovsø Søs , Kolic Jelena , MacDonald Patrick E. , Johnson James D. 
Published: June 2023

AbstractPancreatic β-cells are critical for systemic glucose homeostasis, and most of them undergo cell death during the pathogenesis of type 1 diabetes. We previously showed that a Na+channel inhibitor, carbamazepine, could protect β-cellsin vitroandin vivo. Here, we confirmed the effects of carbamazepine and other Na+channel inhibitors on human islets and focused on the specific role of the Na+channel gene,Scn9a(Nav1.7), in β-cell function and survival. BecauseScn9acan be found in multiple human and mouse islet cell types, we generated a β-cell specific knockout ofScn9aon the non-obese diabetic (NOD) background. We crossed anScn9aflox/floxallele onto theIns1Creknock-in mouse line resulting in the following genotypes: knockout (NOD.Ins1Cre;Scn9aflox/flox), heterozygous (NOD.Ins1Cre;Scn9aflox/wt), and wildtype littermate controls (NOD.Ins1Cre;Scn9awt/wt). We observed near complete ablation of Na+currents in knockout β-cells, and intermediate Na+currents in the heterozygotes. Insulin secretion in response to 15 mM glucose, but not lower concentrations, was significantly reduced from NOD.Ins1Cre;Scn9aflox/floxand NOD.Ins1Cre;Scn9awt/wtislets from both male and female mice. These effects of carbamazepine on insulin secretionin vitrowere not additive to the effects ofScn9aknockout, suggesting thatScn9ais the main target of carbamazepine in β-cells that is relevant for insulin secretion. CompleteScn9adeletion also protected β-cells from deathin vitro, similarly and non-additively to carbamazepine treatment. Finally, we assessed diabetes incidence in Nod.Scn9aflox/floxmice and NOD.Ins1Cre;Scn9awt/wtmice injected with AAV8-Ins1Crevirus and a found significant reduction in diabetes incidence in β-cell specific knockout mice compared with littermate controls. Collectively, our data show theScn9aplays important roles in β-cell function, but also contributes to β-cell death and type 1 diabetes progression.Scn9ais a novel drug target to preserve β-cells in type 1 diabetes.
Global seasonal activities of respiratory syncytial virus before the COVID-19 pandemic: a systematic review
Authors: Shan Songwei , Zhang Weixin , Gao Huizhi , Huang Pei-Yu , Du Zhanwei , Bai Yuan , Lau Yiu-Chung , Chen Dongxuan , Lau Eric HY , Nealon Joshua , Wu Peng 
Published: June 2023

ABSTRACTBackgroundVaried seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We aimed to review the patterns of RSV activity globally before the COVID-19 pandemic and to explore factors potentially associated with RSV seasonality.MethodsWe conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. Information on the timing of the start, peak, and end of an RSV season, study location, study period, and details in study methods were extracted. RSV seasonal patterns were examined by geographic location, calendar month, analytic method and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations.ResultsRSV seasons were reported in 209 articles published in 1973-2023 for 317 locations in 77 countries. Variations were identified in types of data, data collection and analytical methods across the studies. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Durations of RSV seasons were relatively longer in subtropical and tropical regions than from temperate regions. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity.ConclusionsThe global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection. Heterogeneity in study methods highlighted the importance of developing and applying standardized approaches in RSV surveillance and data reporting.
Engineering of human myotubes toward a mature metabolic and contractile phenotype
Authors: Dreher Simon I. , Grubba Paul , von Toerne Christine , Moruzzi Alessia , Maurer Jennifer , Goj Thomas , Birkenfeld Andreas L. , Peter Andreas , Loskill Peter , Hauck Stefanie M. , Weigert Cora 
Published: June 2023

1.AbstractSkeletal muscle mediates the beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current human skeletal muscle modelsin vitroare incapable of fully recapitulating its physiological functions especially muscle contractility. By supplementation of insulin-like growth factor 1 (IGF1), a growth factor secreted by myofibers in vivo, we aimed to overcome these limitations. We monitored the differentiation process starting from primary human CD56-positive myoblasts in the presence/absence of IGF1 in serum-free medium in daily collected samples for 10 days. IGF1-supported differentiation formed thicker multinucleated myotubes showing physiological contraction upon electrical pulse stimulation following day 6. Myotubes without IGF1 were almost incapable of contraction. IGF1-treatment shifted the proteome toward skeletal muscle-specific proteins that contribute to myofibril and sarcomere assembly, striated muscle contraction, and ATP production. ElevatedPPARGC1A, MYH7 and reduced MYH1/2 suggest a more oxidative phenotype further demonstrated by higher abundance of proteins of the respiratory chain and elevated mitochondrial respiration. IGF1-treatment also upregulated GLUT4 and increased insulin-dependent glucose uptake compared to myotubes differentiated without IGF1.To conclude, utilizing IGF1, we engineered human myotubes that recapitulate the physiological traits of skeletal musclein vivosuperior to established protocols and overcome limitations of previous standards. This novel “easy to use” model enables investigation of exercise on a molecular level.Abstract Figure
Vestibular mapping of the naturalistic head-centered motion spectrum
Authors: Ertl Matthias , Eulenburg Peter zu , Woller Marie , Mayadali Ümit , Boegle Rainer , Dieterich Marianne 
Published: June 2023

AbstractBACKGROUNDNaturalistic head accelerations can be used to elicit vestibular evoked potentials (VestEPs). These potentials allow for analysis of cortical vestibular processing and its multi-sensory integration with a high temporal resolution.METHODSWe report the results of two experiments in which we compared the differential VestEPs elicited by randomized translations, rotations, and tilts in healthy subjects on a motion platform.RESULTSAn event-related potential (ERP) analysis revealed that established VestEPs were verifiable in all three acceleration domains (translations, rotations, tilts). A further analysis of the VestEPs showed a significant correlation between rotation axes (yaw, pitch, roll) and the amplitude of the evoked potentials. We found increased amplitudes for rotations in the roll compared to the pitch and yaw plane. A distributed source localization analysis showed that the activity in the cingulate sulcus visual (CSv) area best explained direction-dependent amplitude modulations of the VestEPs, but that the same cortical network (posterior insular cortex, CSv) is involved in processing vestibular information, regardless of the motion direction.CONCLUSIONThe results provide evidence for an anisotropic, direction-dependent processing of vestibular input by cortical structures. The data also suggest that area CSv plays an integral role in ego-motion perception and interpretation of spatial features such as acceleration direction and intensity.
Designing function-specific minimal microbiomes from large microbial communities
Authors: Raghu Aswathy K. , Palanikumar Indumathi , Raman Karthik 
Published: June 2023

AbstractMotivationMicroorganisms thrive in large communities of diverse species, exhibiting various functionalities. The mammalian gut microbiome, for instance, has the functionality of digesting dietary fibre and producing different short-chain fatty acids. Not all microbes present in a community contribute to a given functionality; it is possible to find aminimalmicrobiome, which is a subset of the large microbiome, that is capable of performing the functionality while maintaining other community properties such as growth rate. Such a minimal microbiome will also contain keystone species for SCFA production in that community. In the wake of perturbations of the gut microbiome that result in disease conditions, cultivated minimal microbiomes can be administered to restore lost functionalities.ResultsIn this work, we present a systematic algorithm to design a minimal microbiome from a large community for a user-proposed function. We employ a top-down approach with sequential deletion followed by solving a mixed-integer linear programming problem with the objective of minimising theL1-norm of the membership vector. We demonstrate the utility of our algorithm by identifying the minimal microbiomes corresponding to model communities of the gut, and discuss their validity based on the presence of the keystone species in the community. Our approach is generic and finds application in studying a variety of microbial communities.AvailabilityThe algorithm is available fromhttps://github.com/RamanLab/minMicrobiomeAuthor SummaryMicroorganisms are ubiquitous in nature. They survive in communities by interacting with each other and influence the biosphere by carrying out specific functions. For instance, the mammalian digestive system is heavily dependent on microbial communities in the gut (known as gut microbiome) to digest dietary fibres which are otherwise indigestible. The capability of gut microbes to convert dietary fibres to short-chain fatty acids help the host by regulating the functionality of the gut epithelial barrier. Oftentimes, some members of a community have redundant functions. Hence, it is possible to find a smaller subset of organisms that is capable of a given functionality, while also maintaining the required growth rate. We call them a minimal microbiome. Knowledge of such function-specific minimal microbiomes is useful for constructing communities for laboratory study and for designing treatment strategies for medical conditions caused by microbiome disruption. We present an optimization algorithm for identifying function-specific minimal microbiomes from a large community. We also demonstrate the performance of the algorithm by analysing minimal microbiomes obtained from some known communities. Overall, our research work highlights the significance of function-specific minimal microbiomes and provides an efficient computational tool for their identification.
The oxygen-induced thiosulfate production during Sulfate reduction, Autotrophic denitrification, Nitrification and Anammox (SANIA) integrated process towards next-generation mainstream wastewater treatment
Authors: Jiang Chu-Kuan , Deng Yang-Fan , Chen Guang-Hao , Wu Di 
Published: June 2023

AbstractThis study proposes a novel integrated process: the oxygen-induced thiosulfate production duringSulfate reduction,Autotrophic denitrification,NItrification andAnammox (SANIA) integrated process, targeting to treat mainstream wastewater after organics capture. Three moving-bed biofilm reactors (MBBRs) were applied for oxygen-induced thiosulfate production during sulfate reduction, mixed sulfide- and thiosulfate-driven partial denitrification and anammox (MSPDA), and nitrification (N), respectively. This study firstly established SANIA with supply of mimic nitrifying effluent to investigated the development of MSPDA (Period I) and subsequently verified SANIA in mainstream condition with implementation of nitrification (Period II). In Period I, the MSPDA-MBBR fed with ERATO-MBBR and mimic nitrifying effluent, was operated for over 300 days. Without inoculation of anammox biomass, the high rates of denitratation and anammox being 2.7 gN/(m2·d) and 2.8 gN/(m2·d), respectively were developed in the bioreactor with the enrichment of anammox bacteria and the coexistence of sulfur-oxidizing bacteria. Batch tests were performed to explore the bioconversion of sulfur and nitrogen compounds in MSPDA with main findings as following: 1) kinetics and pathways of sulfide (S2-➔ S0➔ SO42-) and thiosulfate (S2O32-➔ SO42-) oxidation were revealed; 2) fast denitrification was achieved during oxidation of sulfide and thiosulfate to S0and sulfate, respectively with sufficient nitrite accumulation, supporting the high activity of anammox; 3) nitrite utilization rate of anammox (50.8 mgN/(m2·h)) is higher than sulfur-driven denitritation (12.9−42.6 mgN/(m2·h)), demonstrating the dominance of anammox in nitrogen removal. In Period II, the N-MBBR was set behind MSPDA-MBBR to supply nitrate by recirculation, thus the SANIA system was developed. Afterwards the integrated SANIA system with a short HRT of 4.7 h was continuously operated for over 130 days. Results demonstrated that 90% of COD, 93% of ammonium and 61% of TIN were removed with concentration of COD, ammonium, and TIN below 10 mg/L, 3 mgN/L and 13 mgN/L, respectively in effluent. Combining with organic capture and SANIA for sewage treatment, the energy-neutral and space-efficient treatment of mainstream wastewater is promising.HighlightsA new sulfur-cycle process (SANIA) was developed for sewage treatment.High rates of both denitratation and anammox were developed in MSPDA.Oxidation of TdS (to S0) and S2O32-(to SO42-) in MSPDA boosts nitrite buildup.74−81% of the removed TIN was via anammox in SANIA process.SANIA with a short HRT of 4.7h achieved good effluent qualities for sewage treatment.