Miracle-dz/UniFAR-FTUs huggingface dataset:
Species-Specificity of Transcriptional Regulation and the Response to Lipopolysaccharide in Mammalian Macrophages

Mammalian macrophages differ in their basal gene expression profiles and response to the toll-like receptor 4 (TLR4) agonist, lipopolysaccharide (LPS). In human macrophages, LPS elicits a temporal cascade of transient gene expression including feed forward activators and feedback regulators that limit the response. Here we present a transcriptional network analysis of the response of sheep bone marrow-derived macrophages (BMDM) to LPS based upon RNA-seq at 0, 2, 4, 7, and 24 h post-stimulation. The analysis reveals a conserved transcription factor network with humans, and rapid induction of feedback regulators that constrain the response at every level. The gene expression profiles of sheep BMDM at 0 and 7 h post LPS addition were compared to similar data obtained from goat, cow, water buffalo, horse, pig, mouse and rat BMDM. This comparison was based upon identification of 8,200 genes annotated in all species and detected at >10TPM in at least one sample. Analysis of expression of transcription factors revealed a conserved transcriptional millieu associated with macrophage differentiation and LPS response. The largest co-expression clusters, including genes encoding cell surface receptors, endosome–lysosome components and secretory activity, were also expressed in all species and the combined dataset defines a macrophage functional transcriptome. All of the large animals differed from rodents in lacking inducible expression of genes involved in arginine metabolism and nitric oxide production. Instead, they expressed inducible transporters and enzymes of tryptophan and kynurenine metabolism. BMDM from all species expressed high levels of transcripts encoding transporters and enzymes involved in glutamine metabolism suggesting that glutamine is a major metabolic fuel. We identify and discuss transcripts that were uniquely expressed or regulated in rodents compared to large animals including ACOD1, CXC and CC chemokines, CD163, CLEC4E, CPM, CSF1, CSF2, CTSK, MARCO, MMP9, SLC2A3, SLC7A7, and SUCNR1. Conversely, the data confirm the conserved regulation of multiple transcripts for which there is limited functional data from mouse models and knockouts. The data provide a resource for functional annotation and interpretation of loci involved in susceptibility to infectious and inflammatory disease in humans and large animal species.
3D Digital Anatomic Angioarchitecture of the Rat Spinal Cord: A Synchrotron Radiation Micro-CT Study

Comprehensive analysis of 3D angioarchitecture within the intact rat spinal cord remains technically challenging due to its sophisticated anatomical properties. In this study, we aim to present a framework for ultrahigh-resolution digitalized mapping of the normal rat spinal cord angioarchitecture and to determine the physiological parameters using synchrotron radiation micro-CT (SRμCT). Male SD rats were used in this ex vivo study. After a proportional mixture of contrast agents perfusion, the intact spinal cord covered the cervical spinal from the upper of the 1st cervical vertebra to the 5th lumbar vertebra was harvested and cut into proper lengths within three distinct regions: Cervical 3–5 levels, Thoracic 10–12 levels, Lumbar 3–5 levels spinal cord and examined using SRμCT. This method enabled the replication of the complicated microvasculature network of the normal rat spinal cord at the ultrahigh-resolution level, allowing for the precise quantitative analysis of the vascular morphological difference among cervical, thoracic and lumbar spinal cord in a 3D manner. Apart from a series of delicate 3D digital anatomical maps of the rat spinal cord angioarchitecture ranging from the cervical and thoracic to the lumbar spinal cord were presented, the 3D reconstruction data of SRμCT made the 3D printing of the spinal cord targeted selected microvasculature reality, that possibly provided deep insight into the nature and role of spinal cord intricate angioarchitecture. Our data proposed a new approach to outline systematic visual and quantitative evaluations on the 3D arrangement of the entire hierarchical microvasculature of the normal rat spinal cord at ultrahigh resolution. The technique may have great potential and become useful for future research on the poorly understood nature and function of the neurovascular interaction, particularly to investigate their pathology changes in various models of neurovascular disease.
Cross-Species Insights Into Genomic Adaptations to Hypoxia

Over millions of years, vertebrate species populated vast environments spanning the globe. Among the most challenging habitats encountered were those with limited availability of oxygen, yet many animal and human populations inhabit and perform life cycle functions and/or daily activities in varying degrees of hypoxia today. Of particular interest are species that inhabit high-altitude niches, which experience chronic hypobaric hypoxia throughout their lives. Physiological and molecular aspects of adaptation to hypoxia have long been the focus of high-altitude populations and, within the past decade, genomic information has become increasingly accessible. These data provide an opportunity to search for common genetic signatures of selection across uniquely informative populations and thereby augment our understanding of the mechanisms underlying adaptations to hypoxia. In this review, we synthesize the available genomic findings across hypoxia-tolerant species to provide a comprehensive view of putatively hypoxia-adaptive genes and pathways. In many cases, adaptive signatures across species converge on the same genetic pathways or on genes themselves [i.e., the hypoxia inducible factor (HIF) pathway). However, specific variants thought to underlie function are distinct between species and populations, and, in most cases, the precise functional role of these genomic differences remains unknown. Efforts to standardize these findings and explore relationships between genotype and phenotype will provide important clues into the evolutionary and mechanistic bases of physiological adaptations to environmental hypoxia.
Increased Cerebrospinal Fluid S100B and NSE Reflect Neuronal and Glial Damage in Parkinson’s Disease

Introduction: The diagnosis of Parkinson’s disease (PD) mainly relies on clinical manifestation, but may be difficult to make in very early stages of the disease, especially in pre-motor PD. Thus, there is great interest in finding a biomarker for PD. Among diagnostic biomarkers, the most promising molecules are those which reflect the pathophysiological mechanisms of the disease. Until now, only α-synuclein, a classical CSF Alzheimer’s disease biomarker, and neurofilament light (NFL) chains have turned out to be helpful in differential diagnosis between PD and healthy control subjects. Aim: To assess whether CSF molecules related to some pathological processes present in PD might be of interest in the diagnosis of PD and whether they correlate with disease severity. Methods: CSF levels of S100B and neuron-specific enolase (NSE) were measured in 58 PD patients and in 28 healthy control subjects. Correlations were determined between the levels of these CSF molecules and measures of disease severity (Hoehn–Yahr scale and UPDRS part III), as well as disease duration and levodopa dose. Results: CSF S100B and CSF NSE were both significantly increased in PD subjects vs. healthy controls (p = 0.007 and p = 0.00035, respectively). CSF S100B was significantly positively correlated with measures of disease severity (H-Y score and UPDRS part III), as well as disease duration (p < 0.05). No correlation was found between CSF NSE levels and disease severity or disease duration (p > 0.05). CSF S100B levels alone provided a relatively high discrimination (AUC 0.77) between PD and healthy controls, with 60.7% sensitivity and 88.5% specificity (p < 0.001) at a cut-off value of 123.22 pg/ml. Similarly, CSF NSE levels alone provided a relatively high discrimination (AUC 0.775) between PD and healthy controls, with 78.6% sensitivity and 74.1% specificity at a cut-off value of 51.56 ng/ml (p < 0.001). Conclusions: Our results show that both CSF S100B and CSF NSE seem to be promising markers of the axonal and glial degeneration present in PD. Additionally CSF S100B may be a promising marker of PD progression.
Proteomic Study of Fetal Membrane: Inflammation-Triggered Proteolysis of Extracellular Matrix May Present a Pathogenic Pathway for Spontaneous Preterm Birth

Introduction Spontaneous preterm birth (sPTB), which predominantly presents as spontaneous preterm labor (sPTL) or prelabor premature rupture of membranes (PPROM), is a syndrome that accounts for 5–10% of live births annually. The long-term morbidity in surviving preterm infants is significantly higher than that in full-term neonates. The causes of sPTB are complex and not fully understood. Human placenta, the maternal and fetal interface, is an environmental core of fetal intrauterine life, mediates fetal oxygen exchange, nutrient uptake, and waste elimination and functions as an immune-defense organ. In this study, the molecular signature of preterm birth placenta was assessed and compared to full-term placenta by proteomic profiling. Materials and Methods Four groups of fetal membranes (the amniochorionic membranes), with five cases in each group in the discovery study and 30 cases in each group for validation, were included: groups A: sPTL; B: PPROM; C: full-term birth (FTB); and D: full-term premature rupture of membrane (PROM). Fetal membranes were dissected and used for proteome quantification study. Maxquant and Perseus were used for protein quantitation and statistical analysis. Both fetal membranes and placental villi samples were used to validate proteomic discovery. Results Proteomics analysis of fetal membranes identified 2,800 proteins across four groups. Sixty-two proteins show statistical differences between the preterm and full-term groups. Among these differentially expressed proteins are (1) proteins involved in inflammation (HPGD), T cell activation (PTPRC), macrophage activation (CAPG, CD14, and CD163), (2) cell adhesion (ICAM and ITGAM), (3) proteolysis (CTSG, ELANE, and MMP9), (4) antioxidant (MPO), (5) extracellular matrix (ECM) proteins (APMAP, COL4A1, LAMA2, LMNB1, LMNB2, FBLN2, and CSRP1) and (6) metabolism of glycolysis (PKM and ADPGK), fatty acid synthesis (ACOX1 and ACSL3), and energy biosynthesis (ATP6AP1 and CYBB). Conclusion Our molecular signature study of preterm fetal membranes revealed inflammation as a major event, which is inconsistent with previous findings. Proteolysis may play an important role in fetal membrane rupture. Extracellular matrix s have been altered in preterm fetal membranes due to proteolysis. Metabolism was also altered in preterm fetal membranes. The molecular changes in the fetal membranes provided a significant molecular signature for PPROM in preterm syndrome.
Alterations of Heartbeat Evoked Magnetic Fields Induced by Sounds of Disgust

The majority of the models of emotional processing attribute subjective emotional feelings to physiological changes in the internal milieu, which are sensed by the interoceptive system. These physiological reactions evoked by emotional phenomena occur via the autonomic nervous system, and give rise to alterations in body-mind interactions that are characterized by heartbeat evoked magnetic fields (HEFs) involving brain regions associated with emotional perception. The current study used magnetoencephalography (MEG) to examine regional cortical activity and connectivity changes in HEFs provoked by the emotion of disgust. MEG results from 39 healthy subjects (22 female) revealed that passively listening to sounds of disgust elicited right insular cortical activity and enhancement of cortical connectivity between the right anterior ventral insular cortex and left ventromedial prefrontal cortex, demonstrated by phase lag indexes in the beta frequency range. Furthermore, inter-trial coherence significantly increased at 19 Hz and 23 Hz, and decreased at 14 Hz, which highlights the involvement of low beta oscillations in emotional processing. As these results were based on spontaneously triggered bioelectrical signals, more indigenous and induced signals were extracted with a block designed experiment. The insular cortices play an important role in emotional regulation and perception as the main cortical target for signals with interoceptive information, providing direct substrates of emotional feelings. The current results provide a novel insight into frequency properties of emotional processing, and suggest that emotional arousal evoked by listening to sounds of disgust partially impact the autonomic nervous system, altering HEFs via connectivity changes in the right anterior ventral insular cortex and left ventromedial prefrontal cortex.
microRNAs Shape Myeloid Cell-Mediated Resistance to Cancer Immunotherapy

Immunotherapy with immune checkpoint inhibitors can achieve long-term tumor control in subsets of patients. However, its effect can be blunted by myeloid-induced resistance mechanisms. Myeloid cells are highly plastic and physiologically devoted to wound healing and to immune homeostasis maintenance. In cancer, their physiological activities can be modulated, leading to an expansion of pro-inflammatory and immunosuppressive cells, the myeloid-derived suppressor cells (MDSCs), with detrimental consequences. The involvement of MDSCs in tumor development and progression has been widely investigated and MDSC-induced immunosuppression is acknowledged as a mechanism hindering effective immune checkpoint blockade. Small non-coding RNA molecules, the microRNAs (miRs), contribute to myeloid cell regulation at different levels, comprising metabolism and function, as well as their skewing to a MDSC phenotype. miR expression can be indirectly induced by cancer-derived factors or through direct miR import via extracellular vesicles. Due to their structural stability and their presence in body fluids miRs represent promising predictive biomarkers of resistance, as we recently found by investigating plasma samples of melanoma patients undergoing immune checkpoint blockade. Dissection of the miR-driven involved mechanisms would pave the way for the identification of new druggable targets. Here, we discuss the role of these miRs in shaping myeloid resistance to immunotherapy with a special focus on immunosuppression and immune escape.
Energy Storage in Supercapacitors: Focus on Tannin-Derived Carbon Electrodes

Supercapacitors (SCs) are energy storage devices that bridge the gap between batteries and conventional capacitors. They can store more energy than capacitors and supply it at higher power outputs than batteries. These features, combined with high cyclability and long-term stability, make SCs attractive devices for energy storage. SCs are already present in many applications, either in combination with other energy storage devices (mainly batteries), or as autonomous energy sources. Porous carbons are presently used in the electrodes of commercial SCs due to their high surface area and their good conductivity. However, new porous materials are continuously being developed. Herein, an outline of the principles of the energy storage mechanism in SCs is presented as a guide to illustrate the research on porous carbons materials for SC applications. Indeed, an overview of these carbons and their synthesis methods is also presented. In the context of an urgent need to progress toward the development of environmentally friendly technologies and methods, the final part of this review focuses on the studies carried out using biosourced carbon precursors, such as tannins, which are natural polyphenolic molecules. In particular, mimosa tannin-derived carbon materials with controlled micro- and mesoporosity can be produced by methods with lower environmental impact and lower health and safety risks because crosslinkers are not needed to produce resins.
Protocol Improvement for RNA Extraction From Compromised Frozen Specimens Generated in Austere Conditions: A Path Forward to Transcriptomics-Pathology Systems Integration

At the heart of the phenome-to-genome approach is high throughput assays, which are liable to produce false results. This risk can be mitigated by minimizing the sample bias, specifically, recycling the same tissue specimen for both phenotypic and genotypic investigations. Therefore, our aim is to suggest a methodology of obtaining robust results from frozen specimens of compromised quality, particularly if the sample is produced in conditions with limited resources. For example, generating samples at the International Space Station (ISS) is challenging because the time and laboratory footprint allotted to a project can get expensive. In an effort to be economical with available resources, snap-frozen euthanized mice are the straightforward solution; however, this method increases the risk of temperature abuse during the thawing process at the beginning of the tissue collection. We found that prolonged immersion of snap frozen mouse carcass in 10% neutral buffered formalin at 4°C yielded minimal microscopic signs of ice crystallization and delivered tissues with histomorphology that is optimal for hematoxylin and eosin (H&E) staining and fixation on glass slides. We further optimized a method to sequester the tissue specimen from the H&E slides using an incubator shaker. Using this method, we were able to recover an optimal amount of RNA that could be used for downstream transcriptomics assays. Overall, we demonstrated a protocol that enables us to maximize scientific values from tissues collected in austere condition. Furthermore, our protocol can suggest an improvement in the spatial resolution of transcriptomic assays.
Physiological integration among tillers of Holcus lanatus: age‐dependence and responses to clipping and competition

summary The ecological consequences of physiological integration among tillers were examined in a glasshouse experiment on the clonal grass Holcus lanatus L. We measured the effects of severing the internode connection between a tiller and its parent on the growth and survival of this marked tiller. The effects of three factors on the response to Severing were determined using this procedure: competition with the parent plant, by comparing tillers repotted in isolation with tillers remaining in the neighborhood of the parent; dipping treatment, comprising no clipping, clipping only the marked tiller and its daughter tillers or clipping the whole parent plant, including the marked tiller; and the change in the response with tiller age at severing, using four tiller ages (1, 2, 4 and 8 wk). These age, clipping and severing treatments wt-re applied factorially. After 8 wk of growth the responses to severing of the marked tillers, were dependent on the age and clipping treatments. Severing always decreased survival and growth (tiller production, biomass and tiller extension) of the youngest tillers (ages 1 and 2wk), indicating that they were dependent on the parent to support their early growth. Age 4 tillers were able to support their own growth and grew hest in isolation; but when grown in the parent's neighbourhood competition with the parent reduced growth, although parental support ameliorated these effects. Some of the oldest tillers (age 8 wk) showed decreased growth when unsevered. This indicated an outflow of resources to the parent and suggested that integration allowed the control and coordination of tiller growth. The pattern of the severing effects was similar in all clipping treatments, varying only in degree. There was little evidence of increased support for clipped tillers or for a change in the pattern of integration when the whole plant was clipped, except that age 8 tillers showed a continued benefit of the connection, in contrast to the positive effect of severing in the other two clipping treatments. The extension rate of the marked tiller showed complex responses to clipping and severing treatments, including effects of integration on regrowth after clipping. This experiment has shown that the growth of tillers in H. lanatus is highly integrated but that this integration is extremely plastic in response to tiller age and, to a lesser extent, clipping treatment.
A Clinician's Guide to Cancer-Derived Exosomes: Immune Interactions and Therapeutic Implications

Understanding of the role of immunity in the regulation of cancer growth continues to rapidly increase. This is fuelled by the impressive results yielded in recent years by immune checkpoint inhibitors, which block regulatory pathways to increase immune-mediated cancer destruction. Exosomes are cell-secreted membranous nanoscale vesicles that play important roles in regulating physiological and pathophysiological processes. Cancer-derived exosomes (CDEXs) and their biologically-active cargos have been proven to have varied effects in malignant progression, including the promotion of angiogenesis, metastasis, and favorable microenvironment modification. More recently, there is an increasing appreciation of their role in immune evasion. In addition to CDEXs, there are immune-derived exosomes that facilitate communication between immune cells in the non-malignant setting. Investigation of cancer-mediated mechanisms behind interruption or modification of these normal exosomal pathways may provide further understanding of how malignant immune evasion is accomplished. Accumulating evidence indicates that immune-active CDEXs also have the potential to impact clinical oncological management. Whilst immune checkpoint inhibitors have well-established pharmacologically-targeted pathways involving the immune system, other widely used treatments such as radiation and cytotoxic chemotherapies do not. Thus, investigating exosomes in immunotherapy is important for the development of next-generation combination therapies. In this article, we review the ways in which CDEXs impact individual immune cell types and how this contributes to the development of immune evasion. We discuss the relevance of lymphocytes and myeloid-lineage cells in the control of malignancy. In addition, we highlight the ways that CDEXs and their immune effects can impact current cancer therapies and the resulting clinical implications.