bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning of the same task subserved by substantially different mechanisms between patients with Body Dysmorphic Disorder and healthy individuals
Authors: Wang Zhiyan , Tan Qingleng , Frank Sebastian M. , Sasaki Yuka , Sheinberg David , Phillips Katharine A. , Watanabe Takeo 
Published: December 2023

AbstractIt is generally believed that learning of a perceptual task involving low-level neuronal mechanisms is similar between individuals. However, it is unclear whether this assumption also applies to individuals with psychiatric disorders that are known to have altered brain activation during visual processing. We investigated this question in patients with body dysmorphic disorder (BDD), a psychiatric disorder characterized by distressing or impairing preoccupation with nonexistent or slight defects in one’s physical appearance, and in healthy controls. Participants completed six training sessions on separate days on a visual detection task for human faces with low spatial frequency (LSF) components. Brain activation during task performance was measured with functional magnetic resonance imaging (fMRI) on separate days prior to and after training. The behavioral results showed that both groups of participants improved on the visual detection task to a similar extent through training. Despite this similarity in behavioral improvement, neuronal changes in the Fusiform Face Area (FFA), a core cortical region involved in face processing, with training were substantially different between groups. First, activation in the right FFA for LSF faces relative to High Spatial Frequency (HSF) faces that were used as an untrained control increased after training in BDD patients but decreased in controls. Second, resting state functional connectivity between left and right FFAs decreased after training in BDD patients but increased in controls. Contrary to the assumption that learning of a perceptual task is subserved by the same neuronal mechanisms across individuals, our results indicate that the neuronal mechanisms involved in learning of a face detection task differ fundamentally between patients with BDD and healthy individuals. The involvement of different neuronal mechanisms for learning of even simple perceptual tasks in patients with BDD might reflect the brain’s adaptations to altered functions imposed by the psychiatric disorder.
Parkinson’s disease-related Miro1 mutation induces mitochondrial dysfunction and loss of dopaminergic neuronsin vitroandin vivo
Authors: Chemla Axel , Arena Giuseppe , Sacripanti Ginevra , Barmpa Kyriaki , Zagare Alise , Garcia Pierre , Antony Paul , Ohnmacht Jochen , Baron Alexandre , Jung Jaqueline , Marzesco Anne-Marie , Buttini Manuel , Schmidt Thorsten , Grünewald Anne , Schwamborn Jens C. , Krüger Rejko , Saraiva Claudia 
Published: December 2023

AbstractThe complex and heterogeneous nature of Parkinson’s disease (PD) is still not fully understood, however, increasing evidence supports mitochondrial impairments as a major driver of neurodegeneration in PD. Recently, the regulator of mitochondrial homeostasis Miro1 has been linked genetically and pathophysiologically to PD. Using 2D and 3D patient-based induced pluripotent stem cells models, including an isogenic control, showed that the Miro1 p.R272Q mutation leads to mitochondrial impairments including increased oxidative stress, disrupted mitochondrial bioenergetics and altered metabolism. This was accompanied by increased α-synuclein levels in 2D dopaminergic neurons and by a significant reduction of dopaminergic neurons within midbrain organoids. Knock-in mice expressing mutant p.R285Q Miro1 (orthologue of the human p.R272Q mutation) confirmed the PD-specific dopaminergic neuronal loss in the substantia nigra, accumulation of striatal phosphorylated α-synuclein accompanied by behavioral alterations. These findings demonstrate that mutant Miro1 is sufficient to comprehensively model PD-relevant phenotypesin vitroandin vivo, reinforcing its pivotal role in PD pathogenesis.
Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer’s Disease Independent of Amyloid and Tau Pathology
Authors: Kotredes Kevin P. , Pandey Ravi S. , Persohn Scott , Elderidge Kierra , Burton Charles P , Miner Ethan W. , Haynes Kathryn A. , Santos Diogo Francisco S. , Williams Sean-Paul , Heaton Nicholas , Ingraham Cynthia M. , Lloyd Christopher , Garceau Dylan , O’Rourke Rita , Herrick Sarah , Rangel-Barajas Claudia , Maharjan Surendra , Wang Nian , Sasner Michael , Lamb Bruce T. , Territo Paul R. , Sukoff Rizzo Stacey J. , Carter Gregory W. , Howell Gareth R. , Oblak Adrian L. 
Published: December 2023

Structured AbstractINTRODUCTIONMODEL-AD is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to more accurately mimic LOAD than commonly used transgenic models.METHODSWe created the LOAD2 model by combining APOE4, Trem2*R47H, and humanized amyloid-beta. Mice aged up to 24 months were subjected to either a control diet or a high-fat/high-sugar diet (LOAD2+HFD) from two months of age. We assessed disease-relevant outcomes, including in vivo imaging, biomarkers, multi-omics, neuropathology, and behavior.RESULTSBy 18 months, LOAD2+HFD mice exhibited cortical neuron loss, elevated insoluble brain Aβ42, increased plasma NfL, and altered gene/protein expression related to lipid metabolism and synaptic function. In vivo imaging showed age-dependent reductions in brain region volume and neurovascular uncoupling. LOAD2+HFD mice also displayed deficits in acquiring touchscreen-based cognitive tasks.DISCUSSIONCollectively the comprehensive characterization of LOAD2+HFD mice reveal this model as important for preclinical studies that target features of LOAD independent of amyloid and tau.
The role of kinesthetic and visuospatial cues in pain-induced movement avoidance
Authors: Fuchs Xaver , Heed Tobias 
Published: December 2023

AbstractBackgroundAvoidance of movements is an important factor in chronic pain. Previous experiments have investigated the involved learning mechanisms by pairing movements with painful stimuli but, usually, other visuospatial cues are concurrently presented during learning. Therefore, participants might primarily avoid these visuospatial rather than the movement-related cues, potentially invalidating related interpretations of pain-induced movement avoidance. Here, we separated kinesthetic from visuospatial cues to investigate their respective contribution to avoidance learning.MethodsParticipants used a hand-held robotic manipulandum and, during an acquisition phase, received painful stimuli when performing center-out movements. Pain stimuli could be avoided by choosing a curved rather than direct movement trajectories. To distinguish the contribution of kinesthetic vs. visuospatial cues we used two generalization contexts: either participants executed novel movements passing through the same location at which pain had previously been presented in the acquisition phase; or they executed the same pain-associated movements after having been reseated, so that the hand did not pass through the pain-associated location.ResultsAvoidance generalization was comparable in both contexts, and remarkably, highly correlated between them. Our findings suggest that both visuospatial and kinesthetic cues available during acquisition were associated with pain and led to avoidance.ConclusionsOur research corroborates the fear-avoidance pain model and previous studies’ findings that pain can become associated with movements. However, our study indicates that visuospatial cues also play a critical role. Future studies should distinguish movement-related and space-related associations in pain learning.SignificanceChronic pain is a significant health issue typically attributed to maladaptive learning of pain-movement associations and movement avoidance. We demonstrate that visual cues can play a similarly important role as movement cues in pain learning. This aspect has not previously been considered and has likely confounded previous research findings.
Structural basis for human mitochondrial tRNA maturation
Authors: Meynier Vincent , Hardwick Steven W. , Catala Marjorie , Roske Jonas , Oerum Stephanie , Chirgadze Dimitri Y. , Barraud Pierre , Yu Wyatt , Luisi Ben F. , Tisné Carine 
Published: December 2023

AbstractThe human mitochondrial genome is transcribed into two RNAs, containing mRNAs, rRNAs and tRNAs, all dedicated to produce essential proteins of the respiratory chain. The precise excision of tRNAs by the mitochondrial endoribonucleases (mt-RNase), mt-RNase P and Z, releases all RNA species from the two RNA transcripts. The tRNAs then undergo 3’-CCA addition. In metazoan mitochondria, RNase P is a multi-enzyme assembly that comprises the endoribonuclease PRORP and a tRNA methyltransferase subcomplex. The requirement for a tRNA methyltransferase complex in mt-RNase P cleavage activity is not fully understood. Moreover, the mechanisms of pre-tRNA 3’-cleavage and CCA addition have also yet to be uncovered. Here we report cryo-EM structures that visualise these events, revealing the molecular basis for the first steps of RNA-transcript processing in human mitochondria. Altogether, the structures visualise four steps of mitochondrial tRNA maturation: 5’ and 3’ tRNA-end processing, methylation and 3’-CCA addition, and explain the defined sequential order of tRNA processing. The methyltransferase subcomplex recognises the pre-tRNA in a distinct mode that can support tRNA processing and 3’-CCA addition, likely resulting from an evolutionary adaptation of mitochondrial tRNA maturation complexes to the structurally-variable mitochondrial tRNAs. This subcomplex can also ensure a tRNA-folding quality-control checkpoint before the sequential docking of the maturation enzymes.
The last days ofAporia crataegi(L.) in Britain: evaluating genomic erosion in an extirpated butterfly
Authors: Whitla Rebecca , Hens Korneel , Hogan James , Martin Geoff , Breuker Casper , Shreeve Timothy G. , Arif Saad 
Published: December 2023

AbstractCurrent rates of habitat degradation and climate change are causing unprecedented declines in global biodiversity. Studies on vertebrates highlight how conservation genomics can be an effective tool to identify and manage threatened populations, but it is unclear how vertebrate derived metrics of genomic erosion translate to invertebrate species, with their markedly different population sizes and life histories. The Black-veined White butterfly (Aporia crataegi)was extirpated from Britain in the 1920s. Here, we sequenced historical DNA from 17 museum specimens collected between 1854-1924 to reconstruct demography and compare levels of genomic erosion between extirpated British and extant European mainland populations. We contrast these results using modern samples of the Common Blue butterfly (Polyommatus icarus); a species with relatively stable demographic trends in Great Britain. We provide evidence for bottlenecks in both these species around the period of post-glacial colonisation of the British Isles. Our results reveal different demographic histories andNefor both species, consistent with their fates in Britain, likely driven by differences in life history, ecology, genome lengths and body size. Despite a difference, by an order of magnitude, in historical effective population sizes (Ne), reduction in genome-wide heterozygosity inA. crataegiwas comparable to that inP. icarus. Symptomatic ofA. crataegi’s disappearance were marked increases in runs-of-homozygosity (RoH), potentially indicative of recent inbreeding, and accumulation of putatively mildly and weakly deleterious variants. Our results support the idea that metrics of inbreeding and accumulation of deleterious mutations could be more informative markers of population or species in decline.
Effect of eye globe and optic nerve morphologies on gaze-induced optic nerve head deformations
Authors: Liu Tingting , Hung Pham Tan , Wang Xiaofei , Girard Michaël J. A. 
Published: December 2023

ABSTRACTPurposeTo investigate the effect of globe and optic nerve (ON) morphologies and tissue stiffnesses on gaze-induced optic nerve head deformations using parametric finite element modeling and a Design of Experiment (DOE) approach.MethodsA custom software was developed to generate finite element models of the eye using 10 morphological parameters: dural radius, scleral, choroidal, retinal, pial, peripapillary border tissue thicknesses, prelaminar tissue depth, lamina cribrosa (LC) depth, ON radius, and ON tortuosity. A 10-factor 2-level full-factorial analysis (1,024 models) was used to predict the effects of each morphological factor and their interactions on LC strains induced by 13° adduction. Subsequently, a further DOE analysis (1,024 models) was conducted to study the effects and potential interactions between the top 5 morphological parameters identified from the initial DOE study and 5 critical tissue stiffnesses.ResultsIn the DOE analysis of 10 morphological parameters, the five most significant factors were ON tortuosity, dural radius, ON radius, scleral thickness and LC depth. Further DOE analysis incorporating biomechanical parameters highlighted the importance of dural and LC stiffness. A larger dural radius and stiffer dura increased LC strains but the other main factors had the opposite effects. Notably, a significant interaction was found between dural radius and dural stiffness.ConclusionsThis study highlights the significant impact of morphological factors on LC deformations during eye movements, with key morphological effects being more pronounced than tissue stiffnesses.
Reconstitution of autophagosomal membrane tethering reveals that Atg11 can bind and cluster vesicles on cargo mimetics
Authors: Andhare Devika , Katzenell Sarah , Najera Sarah I , Bauer Katherine M , Ragusa Michael J 
Published: December 2023

ABSTRACTAutophagy is essential for the degradation of mitochondria from yeast to humans. Mitochondrial autophagy in yeast is initiated when the selective autophagy scaffolding protein Atg11 is recruited to mitochondria through its interaction with the selective autophagy receptor Atg32. This also results in the recruitment of small 30 nm vesicles that fuse to generate the initial autophagosomal membrane. We demonstrate that Atg11 can bind to autophagosomal-like membranes in vitro in a curvature dependent manner via a predicted amphipathic helix. Deletion of the amphipathic helix from Atg11 results in a delay in the formation of mitophagy initiation sites in yeast. Furthermore, using a novel biochemical approach we demonstrate that the interaction between Atg11 and Atg32 results in the tethering of autophagosomal-like vesicles in clusters to giant unilamellar vesicles containing a lipid composition designed to mimic the outer mitochondrial membrane. Taken together our results demonstrate an important role for autophagosomal membrane binding by Atg11 in the initiation of mitochondrial autophagy.
SntB triggers the antioxidant pathways to regulate development and aflatoxin biosynthesis inAspergillus flavus
Authors: Wu Dandan , Yang Chi , Yao Yanfang , Ma Dongmei , Lin Hong , Hao Ling , Xin Wenwen , Ye Kangfu , Sun Minghui , Hu Yule , Yang Yanling , Zhuang Zhenhong 
Published: December 2023

AbstractThe epigenetic reader SntB was identified as an important transcriptional regulator of growth, development, and secondary metabolite synthesis inAspergillus flavus. However, the underlying molecular mechanism is still unclear. In this study,sntBgene deletion (ΔsntB), complementary (Com-sntB), and HA tag fused tosntB(sntB-HA) strains were constructed by using the homologous recombination method, respectively. Our results revealed that deletion ofsntBinhibited the processes of mycelia growth, conidial production, sclerotia formation, aflatoxin synthesis, and ability to colonize host, and the defective phenotype of knockout strain ΔsntBcould be restored in its complementary strain Com-sntB. Chromatin immunoprecipitation sequencing (ChIP-seq) ofsntB-HA and WT, and RNA sequencing (RNA-seq) of ΔsntBand WT strains revealed that SntB played key roles in oxidative stress response ofA. flavus. The function ofcatCgene (encode a catalase) was further analyzed based on the integration results of ChIP-seq and RNA-seq. In ΔsntBstrain, the relative expression level ofcatCwas significantly higher than in WT strain, while a secretory lipase encoding gene (G4B84_008359) was down-regulated. Under the stress of oxidant menadione sodium bisulfite (MSB), the deletion ofsntBobvious down-regulated the expression level ofcatC. After deletion ofcatCgene, the mycelia growth, conidial production, and sclerotia formation were inhibited, while ROS level and aflatoxin production were increased compared to the WT strain. Results also showed that the inhibition rate of MSB to ΔcatCstrain was significantly lower than that of WT group and AFB1 yield of the ΔcatCstrain was significantly decreased than that of WT strain under the stress of MSB. Our study revealed the potential machinery that SntB regulated fungal morphogenesis, mycotoxin anabolism, and fungal virulence through the axle of from SntB to fungal virulence and mycotoxin bio-synthesis, i.e. H3K36me3 modification-SntB-Peroxisomes-Lipid hydrolysis-fungal virulence and mycotoxin bio-synthesis. The results of this study shed light into the SntB mediated transcript regulation pathways of fungal mycotoxin anabolism and virulence, which provided potential strategy for control the contamination ofA. flavusand its aflatoxins.
Phase diversity-based wavefront sensing for fluorescence microscopy
Authors: Johnson Courtney , Guo Min , Schneider Magdalena C. , Su Yijun , Khuon Satya , Reiser Nikolaj , Wu Yicong , Riviere Patrick La , Shroff Hari 
Published: December 2023

AbstractFluorescence microscopy is an invaluable tool in biology, yet its performance is compromised when the wavefront of light is distorted due to optical imperfections or the refractile nature of the sample. Such optical aberrations can dramatically lower the information content of images by degrading image contrast, resolution, and signal. Adaptive optics (AO) methods can sense and subsequently cancel the aberrated wavefront, but are too complex, inefficient, slow, or expensive for routine adoption by most labs. Here we introduce a rapid, sensitive, and robust wavefront sensing scheme based on phase diversity, a method successfully deployed in astronomy but underused in microscopy. Our method enables accurate wavefront sensing to less than λ/35 root mean square (RMS) error with few measurements, and AO with no additional hardware besides a corrective element. After validating the method with simulations, we demonstrate calibration of a deformable mirror > 100-fold faster than comparable methods (corresponding to wavefront sensing on the ~100 ms scale), and sensing and subsequent correction of severe aberrations (RMS wavefront distortion exceeding λ/2), restoring diffraction-limited imaging on extended biological samples.
Mutations inGPNMBassociated with Amyloid cutis dyschromica alter intracellular trafficking and processing of GPNMB
Authors: Bogacki Erin C. , Lewis Patrick A. , Herbst Susanne 
Published: December 2023

AbstractAmyloid cutis dyschromica (ACD) is a rare skin condition characterized by focal areas of hyperpigmentation with hypopigmented macules and distinct regions of amyloid deposition. Until recently, the genetic cause of ACD remained unknown. Several studies have since named GPNMB truncation mutations as causal, with protein loss-of-function underlying ACD pathogenesis. GPNMB missense mutations have also been observed in patients, but these are less well characterized; especially on a cellular level. Here, we observed that GPNMB missense mutations implicated in familial ACD show distinct cellular phenotypes that result in impaired protein maturation and processing from the endoplasmic reticulum (ER) to thetrans-Golgi network (TGN), prompting failed trafficking to lysosomes. These missense mutations also show failed secretion of the extracellular fragment of GPNMB, a well-characterized property of the protein. Overall, this work highlights previously undescribed cellular characteristics of GPNMB missense mutations implicated in ACD and helps to better inform the clinically observed phenotypes, as well as underscore GPNMB’s role at melanosomes.
Enzyme Fragment Complementation Driven by Nucleic Acid Hybridization
Authors: Xu Zihan , Zhang Xiaoyu , Pal Chandan , Rozners Eriks , Callahan Brian P. 
Published: December 2023

ABSTRACTA modified protein fragment complementation assay has been designed and validated as a gain-of-signal biosensor for nucleic acid:nucleic acid interactions. The assay uses fragments of NanoBiT, the split luciferase reporter enzyme, that are esterified at their C-termini to steramers, sterol-modified oligodeoxynucleotides. TheDrosophilahedgehog autoprocessing domain, DHhC, served as a self-cleaving catalyst for these bioconjugations. In the presence of ssDNA or RNA with segments complementary to the steramers and adjacent to one another, the two NanoBiT fragments productively associate, reconstituting NanoBiT enzyme activity. NanoBiT luminescence in samples containing nM ssDNA or RNA template exceeded background by 30-fold and as high as 120-fold depending on assay conditions. A unique feature of this detection system is the absence of a self-labeling domain in the NanoBiT bioconjugates. Eliminating that extraneous bulk broadens the detection range from short oligos to full-length mRNA.Abstract Figure
Cerebrovascular-balance relationships reveal mechanisms of neuromotor resilience to dual-task cognitive loading
Authors: Palmer Jacqueline A. , Hazen Emily M. , Billinger Sandra A. 
Published: December 2023

AbstractBACKGROUNDAge-related decline in cerebrovascular health precipitates cognitive dysfunction and can be attenuated by habitual physical activity. Cognitive interference in balance control is well-known clinically and reflects compromised neuromotor resilience. However, whether cerebrovascular health affects cognitive-balance dual-tasking with aging is unclear.METHODSThirty participants (76±4years) completed clinical balance/cognitive testing under single-task and dual-task conditions. Balance performance was assessed as the total distance traversed during a challenging beam walking task. Cognitive performance was assessed as response time (RT) during a working-memory n-back test. Transcranial Doppler ultrasound was used to measure resting middle cerebral artery blood velocity (MCAv). We tested whether MCAv was associated with single-task and dual-task interference (DTI) in balance and cognitive performance and the effects of age and physical activity level on this relationship.RESULTSDuring single-tasking, higher MCAv associated with higher balance function (r=0.40,p=0.033), while no relationship was observed for cognitive performance. Dual-tasking strengthened relationships between MCAv and DTI across domains of balance (r=0.442,p=0.016) and cognition (r=0.328,p=0.089); for cognitive DTI, this effect was driven by individuals ≥75years old (r=0.54,p=0.031). Individuals ≥75years exhibited greater cognitive DTI (p=0.049), yet achieved similar balance DTI compared to those <75. Regardless of age, participants with higher MCAv demonstrated greater dual-task prioritization of balance control over cognitive performance (r=0.410,p=0.030). Physically-active participants with higher MCAv also showed less balance DTI (r=0.621,p=0.003), while there was no relationship in under-active/sedentary individuals or within the cognitive domain.CONCLUSIONSOur results support a key role of cerebrovascular health in neuromotor resilience to cognitive loading, which may emerge earlier in brain aging processes affecting balance control compared to cognition. Cerebrovascular health may support people’s ability to prioritize balance in the face of competing attentional demands, and may mediate the positive effects of physical activity on cortically-mediated balance control.