bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum amyloid A-dependent inflammasome activation and acute injury in a mouse model of experimental stroke
Authors: Yu Jin , Zhu Hong , Taheri Saeid , Lee June-Yong , Diamond David M. , Kirstein Cheryl , Kindy Mark S. 
Published: June 2023

BACKGROUNDSerum amyloid A (SAA) proteins increase dramatically in the blood following inflammation. Recently, SAAs are increased in humans following stroke and in ischemic animal models. However, the impact of SAAs on whether this signal is critical in the ischemic brain remains unknown. Therefore, we investigated the role of SAA and SAA signaling in the ischemic brain.METHODSWildtype and SAA deficient mice were exposed to middle cerebral artery occlusion and reperfusion, examined for the impact of infarct volumes, behavioral changes, inflammatory markers, TUNEL staining, and BBB changes. The underlying mechanisms were investigated using SAA deficient mice, transgenic mice and viral vectors.RESULTSSAA levels were significantly increase following MCAo and mice deficient in SAAs showed reduced infarct volumes and improved behavioral outcomes. SAA deficient mice showed a reduction in TUNEL staining, inflammation and decreased glial activation. Mice lacking acute phase SAAs demonstrated a reduction in expression of the NLRP3 inflammasome and SAA/NLRP3 KO mice showed improvement. Restoration of SAA expression via SAA tg mice or adenoviral expression reestablished the detrimental effects of SAA. A reduction in BBB permeability was seen in the SAA KO mice and anti-SAA antibody treatment reduced the effects on ischemic injury.CONCLUSIONSSAA signaling plays a critical role in regulating NLRP3-induced inflammation and glial activation in the ischemic brain. Blocking this signal will be a promising approach for treating ischemic stroke.GRAPHIC ABSTRACTA graphic abstract is available for this article.
Modeling of mitochondrial genetic polymorphisms reveals induction of heteroplasmy by pleiotropic disease locus MT:10398A>G
Authors: Smullen Molly , Olson Meagan N , Murray Liam F , Suresh Madhusoodhanan , Yan Guang , Dawes Pepper , Barton Nathaniel J , Mason Jivanna N , Zhang Yucheng , Fernandez-Fontaine Aria A , Church George M , Mastroeni Diego , Wang Qi , Lim Elaine T , Chan Yingleong , Readhead Benjamin 
Published: June 2023

AbstractMitochondrial (MT) dysfunction has been associated with several neurodegenerative diseases including Alzheimer’s disease (AD). While MT-copy number differences have been implicated in AD, the effect of MT heteroplasmy on AD has not been well characterized. Here, we analyzed over 1,800 whole genome sequencing data from four AD cohorts in seven different tissue types to determine the extent of MT heteroplasmy present. While MT-heteroplasmy was present throughout the entire MT genome for blood samples, we detected MT-heteroplasmy only within the MT control region for brain samples. We observed that an MT variant 10398A>G (rs2853826) was significantly associated with overall MT-heteroplasmy in brain tissue while also being linked with the largest number of distinct disease phenotypes of all annotated MT variants inMitoMap. Using gene-expression data from our brain samples, our modeling discovered several gene networks involved in mitochondrial respiratory chain and Complex I function associated with 10398A>G. The variant was also found to be an expression quantitative trait loci (eQTL) for the gene MT-ND3. We further characterized the effect of 10398A>G by phenotyping a population of lymphoblastoid cell-lines (LCLs) with and without the variant allele. Examination of RNA sequence data from these LCLs reveal that 10398A>G was an eQTL for MT-ND4. We also observed in LCLs that 10398A>G was significantly associated with overall MT-heteroplasmy within the MT control region, confirming the initial findings observed in post-mortem brain tissue. These results provide novel evidence linking MT SNPs with MT heteroplasmy and open novel avenues for the investigation of pathomechanisms that are driven by this pleiotropic disease associated loci.
Impaired parvalbumin interneurons in the retrosplenial cortex as the cause of sex-dependent vulnerability in Alzheimer’s disease
Authors: Terstege Dylan J. , Ren Yi , Ahn Bo Young , Seo Heewon ,   Alzheimer’s Disease Neuroimaging Initiative, Galea Liisa A. M. , Sargin Derya , Epp Jonathan R. 
Published: June 2023

AbstractAlzheimer’s disease is a debilitating neurodegenerative disorder with no cure and few treatment options. In early stages of Alzheimer’s disease, impaired metabolism, and functional connectivity of the retrosplenial cortex strongly predict future cognitive impairments. Therefore, understanding Alzheimer’s disease-related deficits in the retrosplenial cortex is critical for understanding the origins of cognitive impairment and identifying early treatment targets. Using the 5xFAD mouse model, we discovered early, sex-dependent alterations in parvalbumin-interneuron transcriptomic profiles. This corresponded with impaired parvalbumin-interneuron activity, which was sufficient to induce cognitive impairments and dysregulate retrosplenial functional connectivity. In fMRI scans from patients with mild cognitive impairment and Alzheimer’s disease, we observed a similar sex-dependent dysregulation of retrosplenial cortex functional connectivity and, in post-mortem tissue from subjects with Alzheimer’s disease, a loss of parvalbumin interneurons. Reversal of cognitive deficits by stimulation of parvalbumin interneurons in the retrosplenial cortex suggests that this may serve as a promising novel therapeutic strategy.One Sentence SummaryAltered function, connectivity, and survival of parvalbumin expressing neurons in the retrosplenial cortex in Alzheimer’s Disease.
Methods to Utilize Pulse Wave Velocity to Measure Alterations in Cerebral and Cardiovascular Parameters
Authors: Marshall Andrea G. , Neikirk Kit , Shao Bryanna , Crabtree Amber , Vue Zer , Beasley Heather K. , Garza-Lopez Edgar , Scudese Estevão , Wanjalla Celestine N. , Kirabo Annet , Albritton Claude F , Jamison Sydney , Demirci Mert , Murray Sandra A. , Cooper Anthonya T. , Taffet George E , Hinton Antentor O. , Reddy Anilkumar K. 
Published: June 2023

AbstractAlzheimer’s Disease (AD) is a global health issue, affecting over 6 million in the United States, with that number expected to increase as the aging population grows. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. However, the study of cerebrovascular techniques for AD is still evolving. Here, we provide reproducible methods to measure impedance-based pulse wave velocity (PWV), a marker of arterial stiffness, in the systemic vascular (aortic PWV) and in the cerebral vascular (cerebral PWV) systems. Using aortic impedance and this relatively novel technique of cerebral impedance to comprehensively describe the systemic vascular and the cerebral vascular systems, we examined the sex-dependent differences in 5x transgenic mice (5XFAD) with AD under normal and high-fat diet, and in wild-type mice under a normal diet. Additionally, we validated our method for measuring cerebrovascular impedance in a model of induced stress in 5XFAD. Together, our results show that sex and diet differences in wildtype and 5XFAD mice account for very minimal differences in cerebral impedance. Interestingly, 5XFAD, and not wildtype, male mice on a chow diet show higher cerebral impedance, suggesting pathological differences. Opposingly, when we subjected 5XFAD mice to stress, we found that females showed elevated cerebral impedance. Using this validated method of measuring impedance-based aortic and cerebral PWV, future research may explore the effects of modifying factors including age, chronic diet, and acute stress, which may mediate cardiovascular risk in AD.New and NoteworthyHere, we presented a new technique which is an application of the concept of aortic impedance to determining cerebral impedance. While aortic PWV is typically utilized to study aortic stiffness, we also developed a technique of cerebral PWV to study cerebral vascular stiffness. This method may be useful in improving the rigor of studies that seek to have a dual focus on cardiovascular and cerebral function.
Speech recognition from MEG data using covariance filters
Authors: Verkhlyutov Vitaly , Vvedensky Victor , Gurtovoy Konstantin , Burlakov Evgenii , Martynova Olga 
Published: June 2023

AbstractSpeech recognition from EEG and MEG data is the first step in the development of BCI and AI systems for further use in the decoding of inner speech. Great achievements in this direction have been made with the use of ECoG and stereo-EEG. At the same time, there are few works on this topic on the analysis of data obtained by nonin-vasive methods of brain activity registration. Our approach is based on the evaluation of connections in the sensor space with the extraction of the MEG connectivity pattern specific to a given segment of speech. We tested our method on 7 subjects. In all cases, our processing pipeline was sufficiently reliable and worked either without recognition errors or with few errors. After ”training” the algorithm is able to recognize a fragment of spoken speech in a single presentation. For recognition, we used MEG recording segments of 50-1200 ms from the beginning of the word. A segment of at least 600 ms was required for high-quality recognition. Intervals longer than 1200 ms degraded the quality of recognition. Band-pass filtering of MEG showed that the quality of recognition is higher when using the gamma frequency range compared to the low-frequency range of the analyzed signal.
Solitary Silence and Social Sounds: Music influences mental imagery, inducing thoughts of social interactions
Authors: Herff Steffen A. , Cecchetti Gabriele , Ericson Petter , Cano Estefania 
Published: June 2023

AbstractThe COVID-19 pandemic was accompanied by a marked increase in the use of music listening for self-regulation1. During these challenging times, listeners reported they used music ‘to keep them company’2; indicating that they may have turned to music for social solace3. However, whether this is simply a figure of speech or an empirically observable effect on social thought was previously unclear.In three experiments, six hundred participants were presented with silence or task-irrelevant music in Italian, Spanish, or Swedish while performing a directed mental-imagery task in which they imagined a journey towards a topographical landmark4. To control for a possible effect of vocals on imagined content, the music was presented with or without vocals to the participants, of which half were native speakers and the other half non-speakers of the respective languages.Music, compared to silence, led to more vivid imagination and changes in imagined content. Specifically, social interaction emerged as a clear thematic cluster in participants’ descriptions of their imagined content through Latent Dirichlet Allocation. Moreover, Bayesian Mixed effects models revealed that music significantly increased imagined social content compared to silence conditions. This effect remained robust irrespective of vocals or language comprehension. Using stable diffusion, we generated visualisations of participants’ imagined content. In a fourth experiment, a new group of participants was able to use these visualisations to differentiate between content imagined during music listening and that of the silence condition, but only when listening to the associated music. Results converge to show that music, indeed, can be good company.
Closed-loop optogenetic perturbation of macaque oculomotor cerebellum: evidence for an internal saccade model
Authors: Soetedjo Robijanto , Horwitz Gregory D. 
Published: June 2023

AbstractInternal models are essential for the production of accurate movements. The accuracy of saccadic eye movements is thought to be mediated by an internal model of oculomotor mechanics encoded in the cerebellum. The cerebellum may also be part of a feedback loop that predicts the displacement of the eyes and compares it to the desired displacement in real time to ensure that saccades land on target. To investigate the role of the cerebellum in these two aspects of saccade production, we delivered saccade-triggered light pulses to channelrhodopsin-2-expressing Purkinje cells in the oculomotor vermis (OMV) of two macaque monkeys. Light pulses delivered during the acceleration phase of ipsiversive saccades slowed the deceleration phase. The long latency of these effects and their scaling with light pulse duration are consistent with an integration of neural signals at or downstream of the stimulation site. In contrast, light pulses delivered during contraversive saccades reduced saccade velocity at short latency and were followed by a compensatory reacceleration which caused gaze to land near or on the target. We conclude that the contribution of the OMV to saccade production depends on saccade direction; the ipsilateral OMV is part of a forward model that predicts eye displacement, whereas the contralateral OMV is part of an inverse model that creates the force required to move the eyes with optimal peak velocity for the intended displacement.Significance StatementTheory and experiment suggest that saccade production involves an internal model of oculomotor mechanics that resides inside the cerebellum. How cerebellar neurons implement this model is poorly understood. To illuminate this issue, we stimulated Purkinje cells in the oculomotor vermis (OMV) optogenetically during saccades and examined the resultant movement deviations. Stimulation of the contralateral OMV affected saccade dynamics at short latency, suggesting that the contralateral OMV is part of the feedforward pathway that produces the saccade motor command. In contrast, perturbation of the ipsilateral OMV affected saccade dynamics at longer latency, prolonging the saccade deceleration phase and leading to hypermetria. These effects are consistent with perturbation of the eye displacement integrator in the feedback loop of the saccade generator.
The speed and phase of locomotion dictate saccade probability and simultaneous low-frequency power spectra
Authors: Barnes Lydia , Davidson Matthew J , Alais David 
Published: June 2023

AbstractEveryday we make thousands of saccades and take thousands of steps as we explore our environment. Despite their common co-occurrence in a typical active state, we know little about the coordination between eye-movements and walking behaviour and related changes in cortical activity. Technical limitations have been a major impediment which we overcome here by leveraging the advantages of an immersive wireless virtual reality (VR) environment with three-dimensional position tracking, together with simultaneous recording of eye-movements and mobile electroencephalography (EEG). Using this approach with participants engaged in unencumbered walking along a clear, level path, we find that the likelihood of eye-movements at both slow and natural walking speeds entrains to the rhythm of footfall, peaking shortly after the heel-strike of each step. Simultaneous EEG recordings reveal a concomitant modulation entrained to heel-strike, with increases and decreases in oscillatory power for a broad range of frequencies. The peak of these effects occurred in the theta and alpha range for both walking speeds. Together, our data show that the step-rate of locomotion influences other behaviours such as eye movements and produces related modulations of simultaneous EEG following the same rhythmic pattern. These results reveal gait as an important factor to be considered when interpreting saccadic and time-frequency EEG data in active observers.
Identification of Cerebrospinal Fluid Proteomic Signatures Associated with Intramedullary Surgery Outcome
Authors: Di Weihao , Gu Wentao , Peng Xike , Shou Jiajun , Zhang Yi , Ge Shufei , Zhao Jian , Gu Shixin ,   the Neurospine Group
Published: June 2023

AbstractsImportanceNeurological function recovery after intramedullary microsurgery is susceptible to various factors. Investigating alterations in cerebrospinal fluid (CSF) protein profiles associated with spinal function recovery could provide valuable insights into prognosis and the development of postoperative therapeutic approaches.ObjectiveThe aim of this research was to identify CSF protein sets linked to recovery outcomes of intramedullary microsurgery.DesignThis research is an observational cohort investigation that collected data from August 2020 to March 2023.SettingThe Neurospine group conducted this single-centered cohort research (http://www.chictr.org.cn, registration ID: ChiCTR2300072704). Participants were followed up for 6 months or more. CSF samples were collected pre-and postoperatively. Perioperative treatments, neurological deficits, and rehabilitation therapies were recorded.ParticipantsThe Neurospine group screened adult patients with intramedullary lesions scheduled for surgical intervention. The exclusion criteria included prior spinal surgery, neurological disorders, surgical complications, or relevant medications.ExposuresThe patients underwent standard intramedullary microsurgical procedures, received medications, and underwent assessments. The CSF protein profiles were examined using tandem mass spectrometry.Main outcomes and measuresThe evaluation of spinal function recovery involved various assessments and correlation analysis was performed. In addition, CSF protein features were identified and their clinical associations were assessed using least absolute shrinkage and selection operator (LASSO) regression modeling.ResultsOf the 43 patients who completed follow-up assessments, 23 were women and 20 were men, with a mean age of 42.8±11.8 years. Histological diagnoses confirmed invasive lesions in 20 patients. Twenty-three patients demonstrated stable or improved spinal function, while 20 patients experienced deterioration during the 3rd and 6th month follow-ups. As indicated by the changes in EMS scales (P= 0.02) and JOA scores (P= 0.03), functional prognosis was associated with pathological characteristics. We developed four models using the CSF proteomics datasets of noninvasive and invasive patients. These LASSO regression models exhibited high accuracy in predicting the recovery rates of the corresponding groups (P> 0.99).Conclusions and relevanceThis research demonstrates that lesion sizes and pathological characteristics are significant factors influencing spinal function recovery. The LASSO regression models developed using identified CSF protein variables for invasive and noninvasive patients, respectively, offer novel methods for the prediction of prognosis and the development of therapeutic approaches.
Lifestyles, left atrial structure and function, and cognitive decline in adults with the metabolic syndrome
Authors: Gonzalez Casanova Ines , Alonso-Gómez Ángel M. , Romaguera Dora , Toledo Estefanía , Li Linzi , Fortuny Elena , López Luis , Ramallal Raúl , Salas-Salvadó Jordi , Tojal-Sierra Lucas , Castañer Olga , Alonso Alvaro 
Published: June 2023

AbstractEvidence supports associations of lifestyle–including diet and physical activity—and weight with cognitive functioning, but the pathways responsible for these associations have not been fully elucidated. Because healthier lifestyles have been associated with better left atrial structure and function, which in turn is associated with better cognitive functioning, we tested the hypothesis that left atrial structure and function is a potential mediator of the association between lifestyles and cognition. We included 476 participants with overweight or obesity and metabolic syndrome from three centers in Spain who underwent lifestyle assessment and transthoracic echocardiography at baseline and had repeated measurements of the Trail Making A test, a measure of executive function, at baseline and at the two-year follow-up. We conducted mediation analyses to test if measures of left atrial structure and function mediated associations between adherence to the Mediterranean diet scores, physical activity, or weight at baseline, and two-year change in Trail Making A scores. The analysis did not find an effect between these factors and Trail Making A scores, and no indirect effects mediated through the echocardiographic measurements. The modest sample size in this analysis is a limitation, and larger studies should be conducted to determine potential cardiovascular factors mediating the association between lifestyle and cognition.
Present: flexible neuroscience- and technology-driven frameworks for the study of classroom engagement
Authors: Shatto Conor Lee , Thorp John , Friedman Josh Sterling , Rosario Isabella , Gu Zhuowei , Shi Junsheng , Zhuo Megan , Brown Adam , He Xiaofu , Spagna Alfredo 
Published: June 2023

AbstractClassroom engagement’s impact on academic success is crucial. However, the contributions of affective, cognitive, and behavioral components of engagement remain uncertain. We conducted two studies using non-invasive, research-based approaches to clarify these contributions. Study 1 employed portable EEG headsets to measure cognitive engagement, in-class quizzes assessed content retention, and post-class subjective questionnaires indexed affective engagement by measuring feelings of learning and engagement. Content retention predicted subjective measures, while the EEG theta/beta ratio was negatively related to content retention but positively related to subjective measures. Study 2 featured embedded measures of content retention, confidence, engagement, background knowledge, and indexed behavioral engagement looking at nonverbal behavior quantified via video camera recordings. Confidence and engagement were significantly correlated with each other and with particular facial muscle, gaze direction, and head pose movements. We discuss how these approaches enable real-time studies of classroom engagement and can be integrated to develop neurofeedback interventions.
The first European woolly rhinoceros mitogenomes retrieved from within cave hyena coprolites suggest long-lasting phylogeographic differentiation
Authors: Seeber PA , Palmer Z , Schmidt A , Chagas A , Kitagawa K , Marinova-Wolff E , Tafelmaier Y , Epp LS 
Published: June 2023

SummaryThe woolly rhinoceros (Coelodonta antiquitatis) is an iconic species of the Eurasian Pleistocene megafauna, which was abundant in Eurasia in the Pleistocene until its demise beginning approximately 10,000 years ago. Despite the early recovery of several specimens from well-known European archaeological sites, including its type specimen (Blumenbach 1799), no genomes of European populations were available so far, and all available genomic data originated exclusively from the Siberian population1. Using coprolites of cave hyenas (Crocuta crocuta spelea) recovered from Middle Palaeolithic layers of two caves in Germany (Bockstein-Loch and Hohlenstein-Stadel), we isolated and enriched predator and prey DNA to assemble the first European woolly rhinoceros mitogenomes, in addition to cave hyena mitogenomes. These mitogenomes of European woolly rhinoceros are genetically distinct from the Siberian woolly rhinoceros, and analyses of the more complete mitogenome suggests a split of the populations potentially coinciding with the earliest fossil records of wooly rhinoceros in Europe.