bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network Segregation in Aging Females and Evaluation of the Impact of Sex Steroid Hormones
Authors: Hicks Tracey H. , Magalhães Thamires N. C. , Ballard Hannah K. , Jackson T. Bryan , Cox Sydney J. , Bernard Jessica A. 
Published: October 2022

AbstractMales and females show differential patterns in connectivity in resting-state networks (RSNs) during normal aging, from early adulthood to late middle age. Age-related differences in network integration (effectiveness of specialized communication at the global network level) and segregation (functional specialization at the local level of specific brain regions) may also differ by sex. These differences may be due at least in part to endogenous hormonal fluctuation, such as that which occurs in females during midlife with the transition to menopause when levels of estrogens and progesterone drop markedly. A limited number of studies that have investigated sex differences in the action of steroid hormones in brain networks. Here we investigated how sex steroid hormones relate to age-network relationships in both males and females, with a focus on network segregation. Females displayed a significant quadratic relationship between age and network segregation for the cerebellar-basal ganglia and salience networks. In both cases, segregation was still increasing through adulthood, highest in midlife, and with a downturn thereafter. However, there were no significant relationships between sex steroid hormone levels and network segregation levels in females, and they did not exhibit significant associations between progesterone or 17β-estradiol and network segregation. Patterns of connectivity between the cerebellum and basal ganglia have been associated with cognitive performance and self-reported balance confidence in older adults. Together, these findings suggest that network segregation patterns with age in females vary by network, and that sex steroid hormones are not associated with this measure of connectivity in this cross-sectional analysis. Though this is a null effect, it remains critical for understanding the extent to which hormones relate to brain network architecture.
Natural variability in bee brain size and symmetry revealed by micro-CT imaging and deep learning
Authors: Lösel Philipp D. , Monchanin Coline , Lebrun Renaud , Jayme Alejandra , Relle Jacob , Devaud Jean-Marc , Heuveline Vincent , Lihoreau Mathieu 
Published: October 2022

AbstractAnalysing large numbers of brain samples can reveal minor, but statistically and biologically relevant variations in brain morphology that provide critical insights into animal behaviour, ecology and evolution. So far, however, such analyses have required extensive manual effort, which considerably limits the scope for comparative research. Here we used micro-CT imaging and deep learning to perform automated analyses of 3D image data from 187 honey bee and bumblebee brains. We revealed strong inter-individual variations in total brain size that are consistent across colonies and species, and may underpin behavioural variability central to complex social organisations. In addition, the bumblebee dataset showed a significant level of lateralization in optic and antennal lobes, providing a potential explanation for reported variations in visual and olfactory learning. Our fast, robust and user-friendly approach holds considerable promises for carrying out large-scale quantitative neuroanatomical comparisons across a wider range of animals. Ultimately, this will help address fundamental unresolved questions related to the evolution of animal brains and cognition.Author SummaryBees, despite their small brains, possess a rich behavioural repertoire and show significant variations among individuals. In social bees this variability is key to the division of labour that maintains their complex social organizations, and has been linked to the maturation of specific brain areas as a result of development and foraging experience. This makes bees an ideal model for understanding insect cognitive functions and the neural mechanisms that underlie them. However, due to the scarcity of comparative data, the relationship between brain neuro-architecture and behavioural variance remains unclear. To address this problem, we developed an AI-based approach for automated analysis of brain images and analysed an unprecedentedly large dataset of honey bee and bumblebee brains. Through this process, we were able to identify previously undescribed anatomical features that correlate with known behaviours, supporting recent evidence of lateralized behaviour in foraging and pollination. Our method is open-source, easily accessible online, user-friendly, fast, accurate, and robust to different species, enabling large-scale comparative analyses across the animal kingdom. This includes investigating the impact of external stressors such as environmental pollution and climate change on cognitive development, helping us understand the mechanisms underlying the cognitive abilities of animals and the implications for their survival and adaptation.
Plasticity of the face-hand sensorimotor circuits after a traumatic brachial plexus injury
Authors: de Figueiredo Torres Fernanda , Ramalho Bia Lima , Rodrigues Marcelle Ribeiro , Schmaedeke Ana Carolina , Moraes Victor Hugo , Reilly Karen T. , de Paula Carvalho Raquel , Vargas Claudia D. 
Published: October 2022

AbstractBackgroundTraumatic brachial plexus injury (TBPI) is a potentially debilitating event, that usually affects young men following car or motorbike accidents. TBPI interferes with hand sensorimotor function, is associated with chronic pain, and causes cortical reorganization. Interactions between the somatosensory and motor cortices are of fundamental importance for motor control. The hands and face stand out as regions of high functionality with a privileged interaction existing between them, as reflected by the proximity and extension of their representations. Face-hand sensorimotor interactions have been demonstrated in healthy subjects.ObjectiveThe aim of this study was to investigate changes in the sensorimotor interaction in the hand and between the face and the hand in TBPI patients in order to better understand the plasticity of face-hand sensorimotor circuits following TBPI.MethodThe experimental design consisted of activating the representation of a hand muscle using transcranial magnetic stimulation (TMS) preceded by an electrical stimulation (ES) applied to the hand or face, which allows the investigation of the cortical reorganization resulting from TBPI. In the paradigm called afferent inhibition (AI), the motor evoked potential (MEP) in a target muscle is significantly reduced by a previous peripheral ES. AI can be evoked in short-latency (SAI) or long-latency (LAI) interstimulus intervals. Nine TBPI patients participated: five had partial sensorimotor function in their hands and were evaluated on the injured side (TBPI-I group) and four had complete loss of sensorimotor function in their hands and were evaluated on the uninjured side (TBPI-UI group). A control group (CG) included 18 healthy adults. A detailed clinical evaluation complemented the analysis.ResultsThe results showed preserved hand sensorimotor integration for TBPI patients at SAI intervals, but not at LAI intervals. For the face-to-hand sensorimotor integration, the results showed no inhibition at SAI intervals for the TBPI patients. For LAI intervals, a facilitation effect was observed for the TBPI patients, an effect we termed long afferent facilitation or LAF. LAF positively correlated with results in the Central Sensitization Inventory and in the Disabilities Arm, Shoulder, and Hand questionnaire.ConclusionThese results point to the existence of an inhibitory regulation system between the representations of the face and the hand that seems to be suppressed in TBPI and correlates with pain. Moreover, brain changes arising from TBPI are not restricted to the hemisphere contralateral to the injured limb, but extend to both hemispheres.
Leak current, even with gigaohm seals, can cause misinterpretation of stem-cell derived cardiomyocyte action potential recordings
Authors: Clark Alexander P. , Clerx Michael , Wei Siyu , Lei Chon Lok , de Boer Teun P. , Mirams Gary R. , Christini David J. , Krogh-Madsen Trine 
Published: October 2022

AbstractHuman induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have become an essential tool to study arrhythmia mechanisms. Much of the foundational work on these cells, and the computational models built from the resultant data, has overlooked the contribution of seal-leak current on the immature and heterogeneous phenotype that has come to define these cells. Here, we usein silicoandin vitrostudies to demonstrate how seal-leak current depolarises action potentials (APs), substantially affecting their morphology, even with seal resistances (Rseal) above 1 GΩ. We show that compensation of this leak current is difficult due to challenges with recording accurate measures of Rsealduring an experiment. Using simulation, we show that Rsealmeasures: 1) change during an experiment, invalidating the use of pre-rupture values, and 2) are polluted by the presence of transmembrane currents at every voltage. Finally, we posit the background sodium current in baseline iPSC-CM models imitates the effects of seal-leak current and is increased to a level that masks the effects of seal-leak current on iPSC-CMs. Based on these findings, we make three recommendations to improve iPSC-CM AP data acquisition, interpretation, and model-building. Taking these recommendations into account will improve our understanding of iPSC-CM physiology and the descriptive ability of models built from such data.Key pointsHuman induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an essential tool in the study of cardiac arrhythmia mechanisms.Their immature and heterogeneous action potential phenotype complicates the interpretation of experimental data, and has slowed their acceptance in industry and academia.We suggest that a leak current caused by an imperfect pipette-membrane seal during single-cell patch-clamp experiments is partly responsible for inducing this phenotype.Usingin vitroexperiments and computational modelling, we show that this seal-leak current affects iPSC-CM AP morphology, even under ‘ideal’ experimental conditions.Based on these findings, we make recommendations that should be considered when interpreting, analysing and fitting iPSC-CM data.
Effective NGN2-based neuronal programming of hiPSCs in an automated microfluidic platform
Authors: Angiolillo S , Micheli S , Gagliano O 
Published: October 2022

AbstractNeurodegenerative diseases represent an increasing health burden, with a worrying lack of models recapitulating the hallmarks of the pathology.Recently, lab-on-a-chip technology has opened new reliable alternatives to conventionalin vitromodels able to replicate key aspects of human physiology. For instance, microfluidics allows to mimic the extracellular accumulation of misfolded proteins in the finely controlled microenvironment, thanks to the intrinsic high surface-area-to-volume ratio.Automated microfluidic platforms offer advantages in implementing high-throughput, standardized and parallelized assays, suitable for drug screenings and developing new therapeutic approaches in a cost-effective way.However, the major challenges in the broad application of automated lab-on-a-chip in biological research are the lack of production robustness and ease of use of the devices.Here, we present an automated microfluidic platform able to host the rapid conversion of human induced pluripotent stem cells (hiPSCs) into neurons via NGN2 viral programming in a user-friendly manner.The design of the platform, built with multilayer soft-lithography techniques, shows easiness in the fabrication and assembly thanks to the simple geometry and experimental reproducibility at the same time.The all operations are automatically managed from the cell seeding, medium change, doxycycline-mediated neuronal induction, and selection of the genetically engineered cells, to the analysis, including immunofluorescence assay.Our results show a high-throughput, efficient and homogenous conversion of hiPSCs in neurons in 10 days showing the expression of mature marker MAP2, and calcium signaling. The neurons-on-chip model here described represents a fully automated loop system able to address the challenges in the field of neurodegenerative diseases and improve current preclinical models.
No evidence that analgesic use after COVID-19 vaccination negatively impacts antibody responses
Authors: Lafleur Bonnie J. , White Lisa , Dake Michael D. , Nikolich Janko Z. , Sprissler Ryan , Bhattacharya Deepta 
Published: October 2022

AbstractUptake of mRNA vaccines, especially booster immunizations, against COVID-19 has been lower than hoped, perhaps in part due to their reactogenicity. Analgesics might alleviate symptoms associated with vaccination, but studies to measure their impact on immune responses have been limited to relatively small cohorts. We semi-quantitatively measured antibody responses following COVID-19 vaccination in 2354 human participants surveyed about analgesic use. Participants who used non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen after vaccination showed elevated antibody levels against the receptor binding domain of Spike protein relative to those who did not use analgesics. This pattern was observed for both mRNA-1273 and BNT162b2 and across age groups. Participants who used analgesics more frequently reported fatigue, muscle aches, and headaches than those who did not use painkillers. Amongst participants who reported these symptoms, we observed no statistically significant differences in antibody levels irrespective of analgesic use. These data suggest that antibody levels are elevated as a function of symptoms and inflammatory processes rather than painkiller use per se. Taken together, we find no evidence that analgesic use reduces antibody responses after COVID-19 vaccination. Recommendation of their use to alleviate symptoms might improve uptake of booster immunizations.
Comprehensive single-cell transcriptomic analysis of embryonic melanoblasts uncovers lineage-specific mechanisms of melanoma metastasis and therapy resistance
Authors: Gopalan Vishaka , Day Chi-Ping , Pérez-Guijarro Eva , Chin Sung , Ebersole Jessica , Smith Cari , Simpson Mark , Sassano Antonella , Constantino Maira Alves , Wu Emily , Yang Howard H. , Lee Maxwell P. , Hannenhalli Sridhar , Merlino Glenn , Marie Kerrie L. 
Published: October 2022

AbstractAcross cancers, tumor cells can resemble embryonic cell states that may allow them to metastasize and evade therapies. Melanoma is a cancer of the melanocyte that exhibits a wide range of transcriptional states characterized by alterations in embryonic melanocyte gene expression patterns. How these states and their functions are related to the embryonic precursors of melanocytes, the melanoblasts, is unknown. Here, we present the first high-resolution single-cell RNA-seq profiles of embryonic melanocytic lineages in mice. We discover a diverse array of transcriptional cell states in this lineage and confirm, for the first time at the single-cell level, that melanocytes arise from Schwann-cell precursors (SCPs), a highly plastic cell population, via a newly described intermediate mesenchymal-like state. Via novel computational strategies to map these developmental cell states to metastatic melanoma, we find that SCP-resembling tumors are associated with exclusion of the immune cells and non-response to immune checkpoint blockade. In contrast, a higher mesenchymal profile underlies immune dysfunction and resistance to BRAF-inhibition therapy. We also carry out the first time-resolved single-cell RNA-seq study of early melanoma metastatic colonization, demonstrating that melanoma cells activate a SCP program transiently during early metastatic colonization. Finally, we discover a hybrid lineage state that resembles multiple melanocytic lineages simultaneously and is enriched in melanoma cells during metastatic seeding and in therapy resistance. Our work reveals that the lineage-specific mechanisms underlie melanoma progression/evolution, including early metastatic colonization and therapeutic resistance.
Brain-imaging evidence for compression of binary sound sequences in human memory
Authors: Planton Samuel , Roumi Fosca Al , Wang Liping , Dehaene Stanislas 
Published: October 2022

AbstractAccording to the language of thought hypothesis, regular sequences are compressed in human memory using recursive loops akin to a mental program that predicts future items. We tested this theory by probing memory for 16-item sequences made of two sounds. We recorded brain activity with functional MRI and magneto-encephalography (MEG) while participants listened to a hierarchy of sequences of variable complexity, whose minimal description required transition probabilities, chunking, or nested structures. Occasional deviant sounds probed the participants’ knowledge of the sequence. We predicted that task difficulty and brain activity would be proportional to the complexity derived from the minimal description length in our formal language. Furthermore, activity should increase with complexity for learned sequences, and decrease with complexity for deviants. These predictions were upheld in both fMRI and MEG, indicating that sequence predictions are highly dependent on sequence structure and become weaker and delayed as complexity increases. The proposed language recruited bilateral superior temporal, precentral, anterior intraparietal and cerebellar cortices. These regions overlapped extensively with a localizer for mathematical calculation, and much less with spoken or written language processing. We propose that these areas collectively encode regular sequences as repetitions with variations and their recursive composition into nested structures.
Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity
Authors: Yu Yong , Gao Shihong M. , Guan Youchen , Hu Pei-Wen , Zhang Qinghao , Liu Jiaming , Jing Bentian , Zhao Qian , Sabatini David M , Abu-Remaileh Monther , Jung Sung Yun , Wang Meng C. 
Published: October 2022

ABSTRACTLysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with different longevity mechanisms. We further discovered the lysosomal recruitment of AMPK and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we discovered lysosomal heterogeneity across tissues as well as the specific enrichment of the Ragulator complex on Cystinosin positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity at different levels and provides resources for understanding the contribution of lysosomal protein dynamics to signal transduction, organelle crosstalk and organism longevity.
Morphofunctional evaluation of the adrenal gland in rats submitted to nutritional restriction during pregnancy
Authors: Telles Bruno dos Santos , Rebelato Hércules Jonas , Esquisatto Marcelo Augusto Marretto , Catisti Rosana 
Published: October 2022

AbstractPoor nutrition during pregnancy causes permanent metabolic and/or structural adaptation in offspring. The adrenal gland produces various steroid hormones during pregnancy. Thus, this study aimed to evaluate the influence of diet during pregnancy on the adrenal glands of Wistar rats. For this, 10-week-old pregnant Wistar rats (p, n=15) and non-pregnant rats (np, n=15) were divided into three groups and received a normoproteic control diet (C, 17% casein, n=5), isocaloric low-protein diet (PR, 6% casein, n=5), or 50% calorie restriction (CR, 50% of the diet consumed by group C), over a period of 21 days. On the 21st day of gestation (21dG, p groups) or on the 21st day of diet (np groups), after anesthetic deepening, the right adrenal gland was collected, weighed (total mass), and prepared for inclusion in Paraplast® for histomorphometric and immunohistochemical analysis (Ki-67, glucocorticoid receptors (GR), and mineralocorticoid receptor (MR)) in the different areas of the gland. Data, expressed as the mean ± SD, were evaluated by one-way analysis of variance with Tukey’s post-test (p < 0.05). CR in pregnancy increased the amount of GR, MR, and Ki-67 receptors in the adrenal gland. The npRC group showed highest GR staining compared to the animals that received a normal diet. Protein restriction in pregnancy decreases adrenal MR. The results allowed us to conclude that even without altering the weight of the adrenal glands, the pRC group suffered the most from stress during the study, suggesting that CR associated with pregnancy can cause morphofunctional changes in the adrenal glands.
Transcriptomics in serum and culture medium reveal shared and differential gene regulation in pathogenic and commensalStreptococcus suis
Authors: Fredriksen Simen , Ruijten Suzanne D. E. , Murray Gemma G. R. , Juanpere-Borràs Maria , van Baarlen Peter , Boekhorst Jos , Wells Jerry M. 
Published: October 2022

AbstractStreptococcus suiscolonizes the upper respiratory tract of healthy pigs at high abundance but can also cause opportunistic respiratory and systemic disease. Disease-associatedS. suisreference strains are well studied, but less is known about commensal lineages. It is not known what mechanisms enable someS. suislineages to cause disease while others persist as commensal colonizers, or to what extent gene expression in disease-associated and commensal lineages diverge. In this study we compared the transcriptomes of 21S. suisstrains grown in active porcine serum and Todd-Hewitt yeast broth. These strains included both commensal and pathogenic strains, including several strains of sequence type (ST) 1, which is responsible for most cases of human disease and considered the most pathogenicS. suislineage. We sampled the strains during their exponential growth phase and mapped RNA-sequencing reads to the corresponding strain genomes. We found that the transcriptomes of pathogenic and commensal strains with large genomic divergence were unexpectedly conserved when grown in active porcine serum, but that regulation and expression of key pathways varied. Notably, we observed strong variation of expression across media of genes involved in capsule production in pathogens, and of the agmatine deiminase system in commensals. ST1 strains displayed large differences in gene expression between the two media compared to strains from other clades. Their capacity to regulate gene expression across different environmental conditions may be key to their success as zoonotic pathogens.