bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lamin A precursor localizes to the Z-disc of sarcomeres in the heart and is dynamically regulated in muscle cell differentiation
Authors: Brayson Daniel , Shanahan Catherine M. 
Published: October 2022

The lamin A precursor, prelamin A, requires extensive processing to yield mature lamin A and effect its primary function as a structural filament of the nucleoskeleton. When processing is perturbed, nuclear accumulation of prelamin A is toxic and causes laminopathic diseases such as Hutchinson–Gilford progeria syndrome and cardiomyopathy. However, the physiological role of prelamin A is largely unknown and we sought to identify novel insights about this. Using rodent heart tissue, primary cells and the C2C12 model of myofibrillogenesis, we investigated the expression and localization patterns of prelamin A in heart and skeletal muscle cells. We found that endogenous prelamin A was detectable in mouse heart localized to the sarcomere in both adult mouse heart and isolated neonatal rat cardiomyocytes. We investigated the regulation of prelamin A in C2C12 myofibrillogenesis and found it was dynamically regulated and organized into striations upon myofibril formation, colocalizing with the Z-disc protein α-actinin. These data provide evidence that prelamin A is a component of the sarcomere, underpinning a physiological purpose for unprocessed prelamin A.
This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.
Maternal dietary deficiencies in folates or choline during pregnancy and lactation worsen stroke outcome in 3-month-old male and female mouse offspring
Authors: Clementson McCoy , Hurley Lauren , Coonrod Sarah , Bennett Calli , Marella Purvaja , Pascual Agnes S. , Pull Kasey , Wasek Brandi , Bottiglieri Teodoro , Malysheva Olga , Ca udill Marie A. , Jadavji Nafisa M. 
Published: October 2022

ABSTRACTMaternal one-carbon (1C) metabolism plays an important role in early life programming. There is a well-established connection between the fetal environment and the health status of the offspring. However, there is a knowledge gap on how maternal nutrition impacts stroke outcome in offspring. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3-month-old offspring. Adult female mice were fed a folic acid deficient diet (FADD), choline deficient diet (ChDD), or control diet (CD) prior to pregnancy. They were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a CD and at 2 months of age were subject to ischemic stroke within the sensorimotor cortex via photothrombosis damage. At 3-months-of-age, motor function was measured in offspring and tissue was collected for analysis. Mothers maintained on either a FADD or ChDD had reduced levels of S-adenosylmethionine in liver and S-adenosylhomocysteine in plasma. After ischemic stroke, motor function was impaired in 3-month-old offspring from deficient mothers compared to CD animals. In brain tissue, there was no difference in ischemic damage volume. When protein levels were assessed in brain tissue, there were lower levels of neurodegeneration in males compared to females and betaine levels were reduced in offspring from ChDD mothers. Our results demonstrate that a deficient maternal diet during critical timepoints in neurodevelopment results in worse stroke outcomes. This study emphasizes the importance of maternal diet and the impact it can have on offspring health.
Photoacoustic imaging reveals transient decrease of oxygenation in murine blood due to monoclonal IgG4 antibody
Authors: Khadria Anjul , Paavola Chad D. , Maslov Konstantin , Brown-Augsburger Patricia L. , Grealish Patrick F. , Lozano Emmanuel , Blankenship Ross L. , Cao Rui , Shi Junhui , Beals John M. , Oladipupo Sunday S , Wang Lihong V. 
Published: October 2022

AbstractOver 100 monoclonal antibodies have been approved by the FDA for clinical use; however, a paucity of knowledge exists regarding the injection site behavior of these formulated therapeutics, i.e., the effect of antibody and formulation on the tissue around the injection site and vice versa. In this report, we injected a near-infrared dye-labeled IgG4 isotope control antibody into the subcutaneous space in mouse ears to analyze the injection site dynamics, including quantifying molecular movement. Surprisingly, we discovered that the antibody reduces the local blood oxygen saturation levels in mice after prolonged anesthesia without affecting the total hemoglobin content and oxygen extraction fraction. The local oxygen saturation results open a new pathway to study the functional effects of monoclonal antibodies.
We the Hunted
Authors: Martin Jesse M. , Leece A.B. , Herries Andy I.R. , Baker Stephanie E. , Strait David S. 
Published: October 2022

AbstractClassic depictions of human evolutionary ecology castHomoas predator and other hominins, includingParanthropus robustus,as prey. Such hypotheses rest on a small number of fossils that exhibit evidence of carnivore predation, including the iconic SK 54 cranium from Swartkrans in South Africa. Here we demonstrate that the SK 54 cranium shares its closest affinities withH. erectusrather thanP. robustus.Demonstrating thatHomowas prey for leopards at Swartkrans weakens the historically significant hypothesis thatHomowas better able to avoid predation because of being behaviourally and technologically advanced compared toParanthropus. Subsequent ideas about hominin paleobiology derived from this hypothesis warrant reconsideration.
Cardiac MAO-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control
Authors: Shi Qian , Malik Hamza , Streeter Jennifer , Wang Jinxi , Huo Ran , Crawford Rachel M. , Shih Jean C. , Chen Biyi , Hall Duane , Abel E. Dale , Song Long-Sheng , Anderson Ethan J. 
Published: October 2022

AbstractBackgroundPeople with clinical depression exhibit increased risk for cardiac arrhythmias that could be related to differences in catecholamine metabolism. Emerging studies have implicated a pathophysiologic role for monoamine oxidase (MAO-A), which catalyzes catecholamine metabolism in the heart. MAO-A is the pharmacological target of some classes of anti-depressants. Here, we investigated the relationship between MAO-A activity and arrhythmogenesis.Methods & ResultsTriNetX database analysis of adult patients with depression (n=11,533) revealed that MAO inhibitor (MAOI) treatment is associated with significantly lower risk of arrhythmias compared with selective serotonin reuptake inhibitor (SSRI) treatment (16.7% vs 18.6%, p=0.0002). To determine a mechanistic link between MAO activity and arrhythmia, we utilized a genetically modified mouse model with cardiomyocyte-specific MAO-A deficiency (cMAO-Adef). Compared with wild-type (WT) mice, cMAO-Adefmice had a significant reduction in the incidence (38.9% vs. 77.8%, p=0.0409) and duration (55.33 ± 26.21s vs.163.1 ± 56.38s, p=0.0360) of catecholamine stress-induced ventricular tachyarrhythmias (VT). Reduced VT risk and duration were associated with altered cardiomyocyte Ca2+handling in the cMAO-Adefhearts, including a marked increase in Ca2+reuptake rate, decreased diastolic Ca2+levels, decreased SR Ca2+load and reduced Ca2+spark activity following catecholamine stimulation relative to WT. Further analysis of molecular mechanisms revealed that altered Ca2+handling in the cMAO-Adefhearts was related to decreased catecholamine-induced phosphorylation of Ca2+/calmodulin-dependent kinase II (CaMKII) and ryanodine receptor 2 (RyR2), and increased phosphorylation of phospholamban (PLB).ConclusionsThese findings suggest that MAO-A inhibition in cardiomyocytes mitigates arrhythmogenesis via enhanced Ca2+reuptake that lowers diastolic Ca2+levels thereby diminishing arrhythmic triggers following catecholamine stimulation. Thus, cardiac MAO-A represents a potential target for antiarrhythmic therapy.
Early categorization of social affordances during the visual encoding of bodily stimuli.
Authors: Moreau Q. , Parrotta E. , Pesci U.G. , Era V. , Candidi M 
Published: October 2022

AbstractInterpersonal interactions rely on various communication channels, both verbal and non-verbal, through which information regarding one’s intentions and emotions are perceived. Here, we investigated the neural correlates underlying the visual processing of hand postures conveying social affordances (i.e., hand-shaking), compared to control stimuli such as hands performing non-social actions (i.e., grasping) or showing no movement at all. Combining univariate and multivariate analysis on electroencephalography (EEG) data, our results indicate that occipito-temporal electrodes show early differential processing of stimuli conveying social information compared to non-social ones. First, the amplitude of the Early Posterior Negativity (EPN, an Event-Related Potential related to the perception of body parts) is modulated differently during the perception of social and non-social content carried by hands. Moreover, our multivariate classification analysis (MultiVariate Pattern Analysis - MVPA) expanded the univariate results by revealing early (<200ms) categorization of social affordances over occipito-parietal sites. In conclusion, we provide new evidence suggesting that the encoding of socially relevant hand gestures is categorized in the early stages of visual processing.
Xanomeline restores endogenous nicotinic acetylcholine receptor signaling in mouse prefrontal cortex
Authors: Power Saige K. , Venkatesan Sridevi , Lambe Evelyn K. 
Published: October 2022

AbstractCholinergic synapses in prefrontal cortex are vital for attention, but this modulatory system undergoes substantial pre- and post-synaptic alterations during adulthood. To examine the integrated impact of these changes, we optophysiologically probe cholinergic synapsesex vivo, revealing a clear decline in neurotransmission in middle adulthood. Pharmacological dissection of synaptic components reveals a selective reduction in postsynaptic nicotinic receptor currents. Other components of cholinergic synapses appear stable, by contrast, including acetylcholine autoinhibition, metabolism, and excitation of postsynaptic muscarinic receptors. Pursuing strategies to strengthen cholinergic neurotransmission, we find that positive allosteric modulation of nicotinic receptors with NS9283 is effective in young adults but wanes with age. To boost nicotinic receptor availability, we harness the second messenger pathways of the preserved excitatory muscarinic receptors with xanomeline. This muscarinic agonist and cognitive-enhancer restores nicotinic signaling in older mice significantly, in a muscarinic- and PKC-dependent manner. The rescued nicotinic component regains youthful sensitivity to allosteric enhancement: treatment with xanomeline and NS9283 restores cholinergic synapses in older mice to the strength, speed, and receptor mechanism of young adults. Our results reveal a new and efficient strategy to rescue age-related nicotinic signaling deficits, demonstrating a novel pathway for xanomeline to restore cognitively-essential endogenous cholinergic neurotransmission.
Contrast-free Super-resolution Doppler (CS Doppler) based on Deep Generative Neural Networks
Authors: You Qi , Lowerison Matthew R. , Shin YiRang , Chen Xi , Chandra Sekaran Nathiya Vaithiyalingam , Dong Zhijie , Llano Daniel A. , Anastasio Mark A. , Song Pengfei 
Published: October 2022

AbstractSuper-resolution ultrasound microvessel imaging based on ultrasound localization microscopy (ULM) is an emerging imaging modality that is capable of resolving micron-scaled vessels deep into tissue. In practice, ULM is limited by the need for contrast injection, long data acquisition, and computationally expensive post-processing times. In this study, we present a contrast-free super-resolution Doppler (CS Doppler) technique that uses deep generative networks to achieve super-resolution with short data acquisition. The training dataset is comprised of spatiotemporal ultrafast ultrasound signals acquired from in vivo mouse brains, while the testing dataset includes in vivo mouse brain, chicken embryo chorioallantoic membrane (CAM), and healthy human subjects. The in vivo mouse imaging studies demonstrate that CS Doppler could achieve an approximate 2-fold improvement in spatial resolution when compared with conventional power Doppler. In addition, the microvascular images generated by CS Doppler showed good agreement with the corresponding ULM images as indicated by a structural similarity index of 0.7837 and a peak signal-to-noise ratio of 25.52. Moreover, CS Doppler was able to preserve the temporal profile of the blood flow (e.g., pulsatility) that is similar to conventional power Doppler. Finally, the generalizability of CS Doppler was demonstrated on testing data of different tissues using different imaging settings. The fast inference time of the proposed deep generative network also allows CS Doppler to be implemented for real-time imaging. These features of CS Doppler offer a practical, fast, and robust microvascular imaging solution for many preclinical and clinical applications of Doppler ultrasound.
Environmental DNA concentrations of Japanese eels in relation to habitat characteristics
Authors: Ono Yurika , Hirasaka Katsuya , Myosho Taijun , Fujimoto Shingo , Yagi Mitsuharu 
Published: October 2022

AbstractThe Japanese eel (Anguilla japonica), is listed as “Endangered” by the IUCN. Understanding eel riverine habitat is useful in considering conservation strategies. This study sought to determine the relationship between environmental DNA (eDNA) concentrations derived from Japanese eels, water quality, and river structure in three small rivers in Nagasaki, Japan. eDNA was detected at 14 of 15 sites (93%). The concentration of eDNA in brackish water was significantly higher than that in freshwater and was correlated with water depth. Eel occurrence throughout the river suggests a need to conserve a diversity of habitats.
Task-based attentional and default mode connectivity associated with STEM anxiety profiles among university physics students
Authors: Smith Donisha D. , Meca Alan , Bottenhorn Katherine L. , Bartley Jessica E. , Riedel Michael C. , Salo Taylor , Peraza Julio A. , Laird Robert W. , Pruden Shannon M. , Sutherland Matthew T. , Brewe Eric , Laird Angela R. 
Published: October 2022

AbstractAttentional control theory (ACT) posits that elevated anxiety increases the probability of re-allocating cognitive resources needed to complete a task to processing anxiety-related stimuli. This process impairs processing efficiency and can lead to reduced performance effectiveness. Science, technology, engineering, and math (STEM) students frequently experience STEM-related anxiety, which can interfere with learning and performance and negatively impact student retention and graduation rates. The objective of this study was to extend the ACT framework to investigate the neurobiological associations between STEM-related anxiety and cognitive performance among 123 physics undergraduate students. Latent profile analysis (LPA) identified four profiles of student STEM-related anxiety, including two profiles that represented the majority of the sample (Low STEM Anxiety; 59.3% and High Math Anxiety; 21.9%) and two additional profiles that were not well represented (High STEM Anxiety; 6.5% and High Science Anxiety; 4.1%). Students underwent a functional magnetic resonance imaging (fMRI) session in which they performed two tasks involving physics cognition: the Force Concept Inventory (FCI) task and the Physics Knowledge (PK) task. No significant differences were observed in FCI or PK task performance between High Math Anxiety and Low STEM Anxiety students. During the three phases of the FCI task, we found no significant brain connectivity differences during scenario and question presentation, yet we observed significant differences during answer selection within and between the dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN). Further, we found significant group differences during the PK task were limited to the DAN, including DAN-VAN and within-DAN connectivity. These results highlight the different cognitive processes required for physics conceptual reasoning compared to physics knowledge retrieval, provide new insight into the underlying brain dynamics associated with anxiety and physics cognition, and confirm the relevance of ACT theory for STEM-related anxiety.
Kleptocytosis: A Novel Parasitic Strategy for Accelerated Reproduction via Host Protein Stealing in Varroa destructor
Authors: Ramsey Samuel D. , Cook Steven C. , Gulbronson Connor , vanEngelsdorp Dennis , Evans Jay , Posada Francisco , Sonenshine Daniel 
Published: October 2022

AbstractThe rapid reproductive capacity of Varroa destructor is among the most significant adaptations underpinning its success as a parasite. To exploit their honey bee host, the parasite must rapidly produce offspring that fully develop into adults and mate in an inflexible 9-day window. Inability to meet this deadline brings the foundress mite’s fitness to zero establishing heavy evolutionary pressure to accelerate reproduction & subsequent development of offspring. Our work fills in gaps in our understanding of a key pathway in this process. Varroa have a poorly-understood ability to pass heretofore unidentified host proteins through their body with minimal digestion/degradation. Via Native-PAGE, we were able to confirm that nine proteins shared with honey bee fat body tissue accumulate intact in the eggs of the foundress mite. As such, we hypothesized that the proteins were several egg yolk precursors synthesized and stored in the fat body. Using antibodies raised against honey bee vitellogenin (Vg) we positively identified this egg yolk precursor via SDS-PAGE and subsequent Western Blot. We then analyzed samples of honey bee fat body tissue, gravid Varroa, so called “phoretic” Varroa, and Varroa eggs via HPLC MS/MS to identify the remaining host proteins and determine their relative abundance. We detected egg yolk precursors in the large lipid transfer protein superfamily, in addition to hexamerin storage proteins, and miscellaneous motor/transfer proteins integral to embryonic development (transferrin, myosin heavy chain, and heat shock protein 60). Varroa lack the capacity to produce some of these proteins and instead employ kleptoparasitism on a molecular level to provision their developing ova, a pathway not described in any other host/parasite relationship, hereafter referred to as kleptocytosis. These different families of proteins are normally produced by the female and conveyed to the vitellogenic egg cell through protein specific receptor-mediated pathways. Such pathways would exclude foreign proteins. We hypothesize that the need to rely on a receptor-mediated pathway is circumvented via the specialized nutritive reproductive tissue, the lyrate organ. Through microCT imaging we detail the connection between the developing ovum and this dual-lobed organ. Better understanding of this pathway presents a novel target for Varroa management as the treatment need only accomplish slowing acquisition or deposition of host proteins thereby disrupting the mite’s ability to meet the temporal demand of its host.
Common brain areas for processing physiologically and socially ‘needed’ stimuli
Authors: Bosulu J. , Luo Y. , Hétu S. 
Published: October 2022

ABSTRACTWe looked at the overlap between brain areas related to perception of physiologically and socially (non-physiological) needed stimuli and how they might regulate serotonin levels. First, we conducted separate ALE meta-analyses on published results pertaining to brain activation patterns when participants perceived food while hungry or water while thirsty, and social interactions while being excluded. This allowed us to identify common consistent brain activation patterns for physiological and social needed stimuli. We also looked at significant spatial association between the common network and serotonin receptor distribution. We found that regions within the mid-posterior insula, the anterior cingulate cortex and the caudate are at the intersection of physiological (hunger and thirst) and social (exclusion) aspects of ‘needing’. Furthermore, we found a significant positive spatial correlation between that common network and 5HT4 receptor among serotonin receptors. While this was the highest for serotonin receptors, it was not the highest of all receptors. Our study suggests there is a common brain pattern during the processing of physiologically and socially needed stimuli, and discusses their spatial association with serotonin receptors and its possible implication.
Phenotypic cross-species conservation and cross-generation directionality switching in epigenetic inheritance
Authors: Bhalla Ameek , Sharma Abhay 
Published: October 2022

AbstractEvidence supporting non-DNA sequence-based inheritance in animals has increasingly been described in recent years, often under short-term, intergenerational inheritance or longer, transgenerational epigenetic inheritance (TEI). Existence of the latter, a stronger indicator of germline transmission, though established in invertebrates remains controversial in mammals due to inherent confounding factors. Besides evolutionary conservation, physiological implications of TEI also remain unclear. Leveraging invertebrate evidence of TEI to assess possible instances in mammals, and dissecting already described models to gain further insights are suggested approaches to address uncertainties in non-genetic inheritance. Here, in an unbiased approach, we compared existing transcriptomic data associated with so far available Drosophila models of inter- and trans-, and rodent models of inter-generational inheritance, observed phenotypic cross-species conservation and cross-generation directionality shift therein, and confirmed these observations experimentally in flies. Specifically, previous models of cold and diet induced inheritance in both flies and mice were commonly associated with altered regulation of proteolysis genes. Besides, fly TEI models were in general characterized by opposite phenotypic regulation between inter- and trans-generational offspring. As insulin producing cell (IPC) ablation was also associated with proteolysis gene dysregulation in one of the mouse models, we opted to use genetic ablation of IPCs in flies for the experimental confirmation. Remarkably, the ablation led to transcriptomic alterations across multiple generations, with dysregulated genes showing proteolysis enrichment. Similarly, phenotypic directionality changed in the opposite direction in transgenerational offspring of IPC ablated ancestors. These results support mammalian existence, and physiologically adaptive and maladaptive consequences of germline mediated epigenetic inheritance.