bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eyeball translations affect saccadic eye movements beyond brainstem control
Authors: Kirchner Johannes , Watson Tamara , Bauer Jochen , Lappe Markus 
Published: August 2022

AbstractVision requires that we rotate our eyes frequently to look at informative structures in the scene. Eye movements are planned by the brain but their execution depends on the mechanical properties of the oculomotor plant, i.e, the arrangement of eyeball position, muscle insertions and pulley locations. Therefore, the biomechanics of rotations is sensitive to eyeball translation because it changes muscle levers. Eyeball translations are little researched as they are difficult to measure with conventional techniques. Here we study the effects of eyeball translation on the coordination of gaze rotation by high-speed MRI recordings of saccadic eye movements during blinks, which are known to produce strong translations. We found that saccades during blinks massively overshoot their targets, and that these overshoots occur in a transient fashion such that the eye is back on target at the time the blink ends. These dynamic overshoots were tightly coupled to the eyeball translation, both in time and in size. Saccades made without blinks were also accompanied by small amounts of transient eyeball retraction, the size of which scaled with saccade amplitude. These findings demonstrate the complex interaction between rotation and translation movements of the eye. The mechanical consequences of eyeball translation on oculomotor control should be considered along with the neural implementation in the brain to understand the generation of eye movements and their disorders.
Task-uninformative visual stimuli improve auditory spatial discrimination: the ambiguous contribution of relative reliability
Authors: Cappelloni Madeline S. , Shivkumar Sabyasachi , Haefner Ralf M. , Maddox Ross K. 
Published: August 2022

ABSTRACTThe brain combines information from multiple sensory modalities to interpret the environment. These processes, collectively known as multisensory integration, have been modeled as Bayesian causal inference, which proposes that perception involves the combination of information from different sensory modalities based on their reliability and their likelihood of stemming from the same causes in the outside world. Bayesian causal inference has explained a variety of multisensory effects in simple tasks but is largely untested in complex sensory scenes where multisensory integration can provide the most benefit. Recently, we presented data challenging the ideal Bayesian model from a new auditory spatial discrimination task in which spatially aligned visual stimuli improve performance despite providing no information about the correct response. Here, we tested the hypothesis that, despite deviating from the ideal observer, the influence of task-uninformative stimuli was still dependent on the reliabilities of auditory and visual cues. We reasoned shorter stimulus durations should lead to less reliable auditory spatial encoding, and hence stronger effects of more reliable visual cues, which are easily localized even at short durations. While our results replicated the effect from our previous study across a wide range of stimulus durations, we did not find a significant increase in effect size with shorter stimuli, leaving our principal question not fully answered.
Perturbations of the T-cell immune repertoire in kidney transplant rejection
Authors: Sigdel Tara K. , Fields Paul A. , Liberto Juliane , Damm Izabella , Kerwin Maggie , Hood Jill , Towfighi Parhom , Sirota Marina , Robins Harlan S. , Sarwal Minnie M. ,   the CMV Systems Immunobiology Group
Published: August 2022

AbstractIn this cross-sectional and longitudinal analysis of mapping the T-cell repertoire in kidney transplant recipients, we have investigated and validated T-cell clonality, immune repertoire chronology at rejection, and contemporaneous allograft biopsy quantitative tissue injury, to better understand the pathobiology of acute T cell and antibody-mediated kidney transplant rejection. To follow the dynamic evolution of T-cell repertoire changes before and after engraftment and during biopsy-confirmed acute rejection, we sequenced 323 peripheral blood samples from 200 unique kidney transplant recipients, with (n=100) and without (n=100) biopsyconfirmed acute rejection. The results of these studies highlight, for the first time, that patients who develop acute allograft rejection, have lower (p=0.01) T cell fraction even before transplantation, followed by its rise after transplantation and at the time of acute rejection accompanied by high TCR repertoire turnover (p=0.004). Acute rejection episodes occurring after the first 6 months post-transplantation, and those with a component of antibody-mediated rejection, had the highest turnover; p=0.0016) of their TCRs. In conclusion, further prospective validation studies are needed to evaluate the clinical utility of peripheral blood TCR analysis for both pre- and post-transplant immune risk assessment and prediction of different mechanisms of graft rejection.
A small-molecule lycorine derivative reveals Na+/K+-ATPase α3 as an anti-obesity target
Authors: Zhou Yunfu , Zhang Henan , Chen Duozhi , Chen Zhangcheng , Li Yongtao , Tian Chenyang , Zhang Cong , Li Cen , Chang Boran , Zeng Rong , Li Jinsong , Song Xiaomin , Chen Yan , Hao Xiaojiang , Li Lin 
Published: August 2022

AbstractObesity poses a global public health challenge and there is a huge unmet medical need for effective and safe anti-obesity therapeutics. Here, we discovered a small-molecule lycorine derivative designated as HLY72 that could potently promote lipolysis and reduce body weight in mice. Further study revealed that Na+/K+-ATPase α3 is the target of HLY72, and the Na+/K+-ATPase inhibitor digitoxin, but not istaroxime which could not go through blood-brain barrier, exhibits similar activities of reducing food intake and promoting lipolysis as HLY72 does in mice. Consistent with these findings, in knockin mice with a digitoxin-binding mutation T807C in Na+/K+-ATPase α3, but not in α1 gene, both digitoxin and HLY72 lose their activities. Furthermore, either chemical inhibition by HLY72 or genetic inhibition by T807C mutation of Na+/K+-ATPase α3 could effectively protect mice from diet-induced obesity. Therefore, we uncovered a previously unknown function of Na+/K+-ATPase α3 in the regulation of lipolysis and energy balance; and revealed a potential treatment and prevention strategy for obesity by targeting Na+/K+-ATPase α3.
High-Resolution 3D Ultra-Short Echo Time MRI with Rosette k-Space Pattern for Brain Iron Content Mapping
Authors: Shen Xin , Özen Ali Caglar , Monsivais Humberto , Sunjar Antonia , Ilbey Serhat , Zheng Wei , Du Yansheng , Chiew Mark , Emir Uzay 
Published: August 2022

AbstractBackgroundThe iron concentration increases during normal brain development and is identified as a risk factor for many neurodegenerative diseases, it is vital to monitor iron content in the brain non-invasively.PurposeThis study aimed to quantify in vivo brain iron concentration with a 3D rosette-based ultra-short echo time (UTE) magnetic resonance imaging (MRI) sequence.MethodsA cylindrical phantom containing nine vials of different iron concentrations (iron (II) chloride) from 0.5 millimoles to 50 millimoles and six healthy subjects were scanned using 3D high-resolution (0.94×0.94×0.94 mm3) rosette UTE sequence at an echo time (TE) of 20 μs.ResultsIron-related hyperintense signals (i.e., positive contrast) were detected based on the phantom scan, and were used to establish an association between iron concentration and signal intensity. The signal intensities from in vivo scans were then converted to iron concentrations based on the association. The deep brain structures, such as the substantia nigra, putamen, and globus pallidus, were highlighted after the conversion, which indicated potential iron accumulations.ConclusionThis study suggested that T1-weighted signal intensity could be used for brain iron mapping.
Cerebellar climbing fibers convey behavioral information of multiplex modalities and form functional modules
Authors: Ikezoe Koji , Hidaka Naoki , Manita Satoshi , Murakami Masayoshi , Tsutsumi Shinichiro , Isomura Yoshikazu , Kano Masanobu , Kitamura Kazuo 
Published: August 2022

AbstractCerebellar climbing fibers (CFs) convey sensorimotor information and their errors, which are used for motor control and learning. Furthermore, they represent reward-related information. Despite such functional diversity of CF signals, it is still unclear whether each CF conveys the information of single or multiple modalities and how the CFs conveying different information are distributed over the cerebellar cortex. We performed two-photon calcium imaging from cerebellar Purkinje cells (PCs) in mice engaged in a voluntary forelimb lever-pull task and demonstrated that CF responses in 93% of PCs could be explained by the combination of multiple behavioral variables, such as lever movement, licking, and reward delivery. Neighboring PCs exhibited similar CF response properties, formed functional clusters, and shared noise fluctuations of responses. Taken together, individual CFs convey behavioral information on multiplex variables and are spatially organized into the functional modules of the cerebellar cortex.
Multisystem Inflammatory Syndrome in Children Managed in the Outpatient Setting: An EHR-based cohort study from the RECOVER program
Authors: Jhaveri Ravi , Webb Ryan , Razzaghi Hanieh , Schuchard Julia , Mejias Asuncion , Bennett Tellen D. , Jone Pei-Ni , Thacker Deepika , Schulert Grant S. , Rogerson Colin , Cogen Jonathan D. , Bailey L. Charles , Forrest Christopher B. , Lee Grace M. , Rao Suchitra 
Published: August 2022

AbstractUsing electronic health record data combined with primary chart review, we identified 7 children across 8 pediatric medical centers with a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) who were managed as outpatients. These findings should prompt a discussion about modifying the case definition to allow for such a possibility.
Deep Learning Restores Speech Intelligibility in Multi-Talker Interference for Cochlear Implant Users
Authors: Borjigin Agudemu , Kokkinakis Kostas , Bharadwaj Hari M. , Stohl Joshua S. 
Published: August 2022

AbstractCochlear implants (CIs) fail to provide the same level of benefit in noisy settings as in quiet. Current noise reduction solutions in hearing aids and CIs only remove predictable, stationary noise, and are ineffective against realistic, non-stationary noise such as multi-talker interference. Recent developments in deep neural network (DNN) models have achieved noteworthy performance in speech enhancement and separation. However, little work has investigated the potential of DNN models in removing multi-talker interference. The research in this regard is even more scarce for CIs. Here, we implemented two DNN models that are well suited for applications in speech audio processing, including (1) recurrent neural network (RNN) and (2) SepFormer. The models were trained with a dataset developed in house (∼30 hours), and then tested with thirteen CI listeners. Both RNN and SepFormer models significantly improved CI listener’s speech intelligibility in noise without compromising the perceived quality of speech. These models not only increased the intelligibility in stationary non-speech noise, but also introduced substantiallymoreimprovements in non-stationaryspeechnoise, where conventional signal processing strategies fall short with little benefits. These results show the promise of using DNN models as a solution for listening challenges in multi-talker noise interference.
Archaic humans have contributed to large-scale variation in modern human T cell receptor genes
Authors: Corcoran Martin , Chernyshev Mark , Mandolesi Marco , Narang Sanjana , Kaduk Mateusz , Sundling Christopher , Färnert Anna , Bernhardsson Carolina , Larena Maximilian , Jakobsson Mattias , Karlsson Hedestam Gunilla B. 
Published: August 2022

AbstractThe human T cell receptor (TCR) genes are critical for mediating immune responses to pathogens, tumors and regulating self-antigen recognition. A detailed analysis and validation of expressed TCR alpha, beta, gamma, and delta genes in 45 donors from 4 human populations: African, East Asian, South Asian, and European, revealed a total of 175 novel TCR variable and junctional alleles. The majority of novel alleles contained coding changes and were present at widely differing frequencies in the populations, a finding confirmed using DNA samples and sequences from the 1000 Genomes Project. Importantly, we identified three Neanderthal-derived, introgressed TCR regions, including a highly divergent novel TRGV4 variant, present in all archaic assemblies, that was frequent in all modern Eurasian population groups. Our results demonstrate significant variation in TCR genes at both individual and population levels, providing a strong incentive for including allelic variation in studies of TCR function in human biology.
Rapid specification of human pluripotent stem cells to functional astrocytes
Authors: Lendemeijer B. , Unkel M. , Mossink B. , Hijazi S. , Sampedro S.G. , Shpak G. , Slump D.E. , van den Hout M.C.G.N. , van IJcken W.F.J. , Bindels E.M.J. , Hoogendijk W.J.G. , Nadif Kasri N. , de Vrij F.M.S. , Kushner S.A. 
Published: August 2022

ABSTRACTAstrocytes are essential for the formation and maintenance of neural networks through metabolic support, facilitation of synaptic function, and optimization of electrophysiological activity. However, a major technical challenge for investigating astrocyte function and disease-related pathophysiology has been the limited ability to obtain functional human astrocytes. Here we present a novel method to efficiently differentiate human pluripotent stem cell (hPSC)-derived neural progenitors to functional astrocytes in 28 days using a culture medium containing leukemia inhibitory factor (LIF) and bone morphogenetic protein 4 (BMP4). This approach yields highly pure populations of astrocytes expressing canonical astrocyte markers, which we confirmed by immunofluorescence, flow cytometry and RNA sequencing. Human PSC-derived astrocytes efficiently buffer glutamate and robustly support neural network activity. Co-cultures of hPSC-derived astrocytes and neurons on multi-electrode arrays generated robust network activity within 2 days and synchronous network bursts after 6 days. Whole cell patch-clamp recordings revealed an increased frequency of postsynaptic currents in human hPSC-derived neurons co-cultured with hPSC-derived versus primary rodent astrocytes, consistent with a corresponding increase in synapse density. Furthermore, hPSC-derived astrocytes retained their hominid morphology when transplanted into a mouse brain. In conclusion, we present a novel protocol to obtain functional astrocytes from human pluripotent stem cells, providing a platform for investigating human astrocyte function and neuronal-glial interactions.
Deciphering therapeutic efficacy of mycosynthesized silver nanoparticles using entomopathogenic fungi Metarhizium anisopliae against MCF-7 breast cancer cells in vitro
Authors: Nambiar Sujisha S , Mohanty Arman , Patra Arupam , Saini Gurvinder Kaur 
Published: August 2022

AbstractGreen synthesis of silver nanoparticles has gained much interest over few decades in the field of biomedical research due to their ease of synthesis, cost effectiveness, enhanced bioactivity and biocompatibility compared to the chemical synthesis. Recent studies on silver nanoparticles have shown their potential in various fields like antimicrobial, anticancer, larvicidal, catalytic, and wound healing properties. In the present study, entomopathogenic fungi Metarhizium anisopliae was used to synthesize silver nanoparticles. These silver nanoparticles were synthesized and characterized using UV-Vis spectroscopy, FESEM, FETEM and FTIR. Compared to the chemically synthesized silver nanoparticles, the mycosynthesized silver nanoparticles (MaAgNP) showed high yield. The size of mycosynthesized silver nanoparticles was found to be 5-20 nm and was spherical in shape. FTIR results confirmed the possible functional groups that are responsible for the reduction of silver ions. The mycosynthesized silver nanoparticles showed cytotoxicity on human breast cancer cell line (MCF-7) and the calculated IC50 value for MaAgNP was found to be 16.50 μg ml-1 whereas the chemically synthesized silver nanoparticles showed cytotoxicity but with increasing concentration, no further significant reduction in cell viability was observed. The possible reason behind improved cytotoxicity of MaAgNP can be the presence of extracellular secondary metabolites present in the fungal filtrate used to synthesize the nanoparticles. The MaAgNP was also observed to induce cell death through reactive oxygen species (ROS) generation.
Common multi-day rhythms in smartphone behavior
Authors: Ceolini Enea , Ghosh Arko 
Published: August 2022

AbstractThe idea that abnormal human activities follow multi-day rhythms spans ancient beliefs centered on the moon to modern clinical observations in epilepsy and mood disorders. Multi-day rhythms remain obscure in normal human activities. To address multi-day rhythms in healthy human behavior we analyzed over 300 million smartphone touchscreen interactions logging up to 2 years of day-to-day activities (N = 401 subjects). By using non-negative matrix factorization and data-driven clustering of ∼1 million periodograms, we captured a range of multi-day rhythms spanning periods from 7 to 52 days – cutting across age and gender. Despite their common occurrence, any given multi-day rhythm was observed in different parts of the smartphone behavior from one person to the next. There was little support in the data for ubiquitous rhythm drivers like the moon. We propose that multiple multi-day rhythms are a common trait, but their consequences may be uniquely experienced in day-to-day behavior.
Organ-Specific Fuel Rewiring in Acute and Chronic Hypoxia Redistributes Glucose and Fatty Acid Metabolism
Authors: Midha Ayush D. , Zhou Yuyin , Queliconi Bruno B. , Barrios Alec M. , Fong Cyril O. Y. , Blecha Joseph E. , VanBrocklin Henry , Seo Youngho , Jain Isha H. 
Published: August 2022

SUMMARYOxygen deprivation can be detrimental. However, chronic hypoxia is associated with decreased incidence of metabolic syndrome and cardiovascular disease in high-altitude populations. Previously, hypoxic fuel rewiring has primarily been studied in immortalized cells. Here, we describe how systemic hypoxia rewires fuel metabolism to optimize whole-body adaptation. Acclimatization to hypoxia coincided with dramatically lower blood glucose and adiposity. Usingin vivofuel uptake and flux measurements, we found that organs partitioned fuels differently during hypoxia adaption. Acutely, most organs increased glucose uptake and suppressed aerobic glucose oxidation, consistent with previousin vitroinvestigations. In contrast, brown adipose tissue and skeletal muscle became “glucose savers,” suppressing glucose uptake by 3-5-fold. Interestingly, chronic hypoxia produced distinct patterns: the heart relied increasingly on glucose oxidation, and unexpectedly, the brain, kidney, and liver increased fatty acid uptake and oxidation. Hypoxia-induced metabolic plasticity carries therapeutic implications for chronic metabolic diseases and acute hypoxic injuries.
Targeted Deletion of Fgf9 in Tendon Disrupts Mineralization of the Developing Enthesis
Authors: Ganji Elahe , Leek Connor , Duncan William , Patra Debabrata , Ornitz David M. , Killian Megan L. 
Published: August 2022

AbstractThe enthesis is a transitional tissue between tendon and bone that matures postnatally. The development and maturation of the enthesis involve cellular processes likened to an arrested growth plate. In this study, we explored the role of fibroblast growth factor 9 (Fgf9), a known regulator of chondrogenesis and vascularization during bone development, on the structure and function of the postnatal enthesis. First, we confirmed spatial expression of Fgf9 in wildtype tendon and enthesis using in situ hybridization. We then used Cre recombinase driven by the scleraxis promoter (ScxCre) to conditionally inactivate Fgf9 in mouse tendon and enthesis. Characterization of enthesis morphology and mechanical properties in Fgf9ScxCre and wildtype (WT) entheses showed a smaller calcaneal and humeral apophyses, thinner cortical bone at the attachment, increased cellularity, and reduced failure load in mature entheses in Fgf9ScxCre compared to WT littermates. During postnatal development, we found reduced chondrocyte hypertrophy and disrupted type X collagen (Col X) in Fgf9ScxCre entheses. These findings support a model in which tendon-derived Fgf9 regulates the functional development of the enthesis, including its postnatal mineralization.
Progression of vascular function and blood pressure in a mouse model of Kawasaki disease
Authors: DelVechio Mia , Alves Juliano V , Saiyi Alina Z , Singh Shubhnita , Galley Joseph , Awata Wanessa M. C. , Bruder-Nascimento Ariane , Bruder-Nascimento Thiago 
Published: August 2022

AbstractBackgroundKawasaki disease (KD) is a systemic vasculitis of childhood characterized by vascular damage in the acute stage, which can persist into the late stage. Aneurysms, myocardial infarction, and death are long-standing complications associated with KD. The vascular mechanisms in the cardiovascular risk of KD are not fully studied. Herein, we investigated the vascular function and blood pressure regulation in a murine model of KD.Material and methodsWe used the Candida albicans water soluble (CAWS) fraction model. Mice were injected with 4 mg CAWS for five consecutive days and separated into 3 groups. Control (Ctrl): water injected for 5 days; CAWS 7 days (C7): CAWS injected for 5 days plus 2 additional days of wait; CAWS 28 days (C28): CAWS injected for 5 days plus 23 additional days of wait. Blood pressure was analyzed via radiotelemetry. In the end, the heart and arteries were harvested for vasculitis characterization and vascular function in a wire myograph. Rat Aortic Vascular Smooth Muscle cells (RASMC) were used to dissect the molecular mechanisms in vitro.Main findingsC7 presented elevated inflammatory markers in the coronary area (CA) and abdominal aortae (AA), whereas C28 showed severe vasculitis in CA and AA. No difference was found in blood pressure and heart rate. Vascular dysfunction characterized by higher contractility to norepinephrine (NA) in C7 and C28 was abolished by blocking nitric oxide (NO) production, reactive oxygen species (ROS), and cyclooxygenase (COX)-derived products. RASMC treated with CAWS (10ug/mL) presented an increase in COX2 expression, which was prevented by pre-treating the cells with TAK-242 [Toll like receptor 4 (TLR4) antagonist, 3x10−5M].ConclusionOur data indicate that the murine model of KD is associated with vascular dysfunction likely dependent on COX-derived products, oxidant properties, and NO bioavailability. Furthermore, VSMC may present an important role in the genesis of vascular dysfunction and vasculitis via the TLR4 pathway. Finally, the CAWS model seems not to be appropriate to study KD-associated shock. More studies are necessary to understand whether vascular dysfunction and COXs are triggers for vasculitis.