Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatocyte growth factor is upregulated in ischemic retina and contributes to retinal vascular leakage and neovascularization

In patients with macular edema due to ischemic retinopathy, aqueous levels of hepatocyte growth factor (HGF) correlate with edema severity. We tested whether HGF expression and activity in mice with oxygen‐induced ischemic retinopathy supports a role in macular edema. In ischemic retina, HGF was increased in endogenous cells and macrophages associated with retinal neovascularization (NV). HGF activator was increased in and around retinal vessels potentially providing vascular targeting. One day after intravitreous injection of HGF, VE‐cadherin was reduced and albumin levels in retina and vitreous were significantly increased indicating vascular leakage. Injection of VEGF caused higher levels of vitreous albumin than HGF, and co‐injection of both growth factors caused significantly higher levels than either alone. HGF increased the number of macrophages on the retinal surface, which was blocked by anti‐c‐Met and abrogated in chemokine (C‐C motif) ligand 2 (CCL2)−/− mice. Injection of anti‐c‐Met significantly decreased leakage within 24 hours and after 5 days it reduced retinal NV in mice with ischemic retinopathy, but had no effect on choroidal NV. These data indicate that HGF is a pro‐permeability, pro‐inflammatory, and pro‐angiogenic factor and along with its activator is increased in ischemic retina providing support for a potential role of HGF in macular edema in ischemic retinopathies.
Protocol for the development of the Master Chemical Mechanism, MCM v3 (Part B): tropospheric degradation of aromatic volatile organic compounds

Kinetic and mechanistic data relevant to the tropospheric degradation of aromatic volatile organic compounds (VOC) have been used to define a mechanism development protocol, which has been used to construct degradation schemes for 18 aromatic VOC as part of version 3 of the Master Chemical Mechanism (MCM v3). This is complementary to the treatment of 107 non-aromatic VOC, presented in a companion paper. The protocol is divided into a series of subsections describing initiation reactions, the degradation chemistry to first generation products via a number of competitive routes, and the further degradation of first and subsequent generation products. Emphasis is placed on describing where the treatment differs from that applied to the non-aromatic VOC. The protocol is based on work available in the open literature up to the beginning of 2001, and some other studies known by the authors which were under review at the time. Photochemical Ozone Creation Potentials (POCP) have been calculated for the 18 aromatic VOC in MCM v3 for idealised conditions appropriate to north-west Europe, using a photochemical trajectory model. The POCP values provide a measure of the relative ozone forming abilities of the VOC. These show distinct differences from POCP values calculated previously for the aromatics, using earlier versions of the MCM, and reasons for these differences are discussed.
The sensitivity of network statistics to incomplete electrode sampling on intracranial EEG

Abstract Network neuroscience applied to epilepsy holds promise to map pathological networks, localize seizure generators, and inform targeted interventions to control seizures. However, incomplete sampling of the epileptic brain because of sparse placement of intracranial electrodes may affect model results. In this study, we evaluate the sensitivity of several published network measures to incomplete spatial sampling and propose an algorithm using network subsampling to determine confidence in model results. We retrospectively evaluated intracranial EEG data from 28 patients implanted with grid, strip, and depth electrodes during evaluation for epilepsy surgery. We recalculated global and local network metrics after randomly and systematically removing subsets of intracranial EEG electrode contacts. We found that sensitivity to incomplete sampling varied significantly across network metrics. This sensitivity was largely independent of whether seizure onset zone contacts were targeted or spared from removal. We present an algorithm using random subsampling to compute patient-specific confidence intervals for network localizations. Our findings highlight the difference in robustness between commonly used network metrics and provide tools to assess confidence in intracranial network localization. We present these techniques as an important step toward translating personalized network models of seizures into rigorous, quantitative approaches to invasive therapy.
Slow 0.1 Hz Breathing and Body Posture Induced Perturbations of RRI and Respiratory Signal Complexity and Cardiorespiratory Coupling

Objective: We explored the physiological background of the non-linear operating mode of cardiorespiratory oscillators as the fundamental question of cardiorespiratory homeodynamics and as a prerequisite for the understanding of neurocardiovascular diseases. We investigated 20 healthy human subjects for changes using electrocardiac RR interval (RRI) and respiratory signal (Resp) Detrended Fluctuation Analysis (DFA, α1RRI, α2RRI, α1Resp, α2Resp), Multiple Scaling Entropy (MSERRI1−4, MSERRI5−10, MSEResp1−4, MSEResp5−10), spectral coherence (CohRRI−Resp), cross DFA (ρ1 and ρ2) and cross MSE (XMSE1−4 and XMSE5−10) indices in four physiological conditions: supine with spontaneous breathing, standing with spontaneous breathing, supine with 0.1 Hz breathing and standing with 0.1 Hz breathing. Main results: Standing is primarily characterized by the change of RRI parameters, insensitivity to change with respiratory parameters, decrease of CohRRI−Resp and insensitivity to change of in ρ1, ρ2, XMSE1−4, and XMSE5−10. Slow breathing in supine position was characterized by the change of the linear and non-linear parameters of both signals, reflecting the dominant vagal RRI modulation and the impact of slow 0.1 Hz breathing on Resp parameters. CohRRI−Resp did not change with respect to supine position, while ρ1 increased. Slow breathing in standing reflected the qualitatively specific state of autonomic regulation with striking impact on both cardiac and respiratory parameters, with specific patterns of cardiorespiratory coupling. Significance: Our results show that cardiac and respiratory short term and long term complexity parameters have different, state dependent patterns. Sympathovagal non-linear interactions are dependent on the pattern of their activation, having different scaling properties when individually activated with respect to the state of their joint activation. All investigated states induced a change of α1 vs. α2 relationship, which can be accurately expressed by the proposed measure—inter-fractal angle θ. Short scale (α1 vs. MSE1−4) and long scale (α2 vs. MSE5−10) complexity measures had reciprocal interrelation in standing with 0.1 Hz breathing, with specific cardiorespiratory coupling pattern (ρ1 vs. XMSE1−4). These results support the hypothesis of hierarchical organization of cardiorespiratory complexity mechanisms and their recruitment in ascendant manner with respect to the increase of behavioral challenge complexity. Specific and comprehensive cardiorespiratory regulation in standing with 0.1 Hz breathing suggests this state as the potentially most beneficial maneuver for cardiorespiratory conditioning.
Endangered Plants in Novel Urban Ecosystems Are Filtered by Strategy Type and Dispersal Syndrome, Not by Spatial Dependence on Natural Remnants

Understanding the contribution of cities to nature conservation is gaining increasing importance with a globally accelerating urbanization and requires insights into the mechanisms that underlie urban distribution patterns. While a considerable number of endangered plant species have been reported for cities, the spatial dependence of populations of these species on natural remnants versus anthropogenic ecosystems is critically understudied due to deficiencies in population distribution data. To which extent endangered species in anthropogenic ecosystems spatially rely on natural remnants is thus an open question. We used a unique dataset of 1,742 precisely mapped populations of 213 endangered plant species in the city of Berlin and related these point data to habitat patches that had been assigned to natural remnants, hybrid ecosystems and novel ecosystems according to the novel ecosystem approach. By applying point pattern analyses (Ripley’s K function, cross K function, cross pair correlation function) we unraveled the spatial dependence of the populations toward the different ecosystem types. Moreover, we tested how plant traits related to plant strategy and dispersal filter for species occurrence across ecosystems. Differentiating populations on anthropogenic sites revealed that populations in hybrid ecosystems spatially depended on natural remnants, but populations in novel ecosystems (i.e. more than a third of all populations) surprisingly didn’t. A conditional inference tree showed that endangered plant species in novel ecosystems are filtered for ruderal strategy type and wind dispersal syndrome, while competitive and stress-tolerant species were mainly confined to natural remnants. Our results highlight the importance of conserving natural remnants as habitats and seed sources of endangered plants. Yet novel urban ecosystems can support many populations of endangered plant species beyond the adjacency to natural remnants, with hybrid ecosystems likely acting as stepping stones. This indicates a specific contribution of urban ecosystems to biodiversity conservation. Since different filters modulate the species pools of different ecosystem types, novel urban ecosystems are not supposed to substitute fully the habitat functions of natural remnants. Our study thus highlights promising opportunities for involving the total range of urban ecosystem types into urban conservation approaches.
CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State

The non-polymorphic nature of CD1 proteins creates a situation in which T cells with invariant T cell receptors (TCRs), like CD1d-specific NKT cells, are present in all humans. CD1b is an abundant protein on human dendritic cells that presents M. tuberculosis (Mtb) lipid antigens to T cells. Analysis of T cell clones suggested that semi-invariant TCRs exist in the CD1b system, but their prevalence in humans is not known. Here we used CD1b tetramers loaded with mycolic acid or glucose monomycolate to study polyclonal T cells from 150 Peruvian subjects. We found that CD1b tetramers loaded with mycolic acid or glucose monomycolate antigens stained TRAV1-2+ GEM T cells or TRBV4-1+ LDN5-like T cells in the majority of subjects tested, at rates ~10-fold lower than NKT cells. Thus, GEM T cells and LDN5-like T cells are a normal part of the human immune system. Unlike prior studies measuring MHC- or CD1b-mediated activation, this large-scale tetramer study found no significant differences in rates of CD1b tetramer-mycobacterial lipid staining of T cells among subjects with Mtb exposure, latent Mtb infection or active tuberculosis (TB) disease. In all subjects, including “uninfected” subjects, CD1b tetramer+ T cells expressed memory markers at high levels. However, among controls with lower mycobacterial antigen exposure in Boston, we found significantly lower frequencies of T cells staining with CD1b tetramers loaded with mycobacterial lipids. These data link CD1b-specific T cell detection to mycobacterial exposure, but not TB disease status, which potentially explains differences in outcomes among CD1-based clinical studies, which used control subjects with low Mtb exposure.
Rheumatoid Arthritis Patients, Both Newly Diagnosed and Methotrexate Treated, Show More DNA Methylation Differences in CD4+ Memory Than in CD4+ Naïve T Cells

Background: Differences in DNA methylation have been reported in B and T lymphocyte populations, including CD4+ T cells, isolated from rheumatoid arthritis (RA) patients when compared to healthy controls. CD4+ T cells are a heterogeneous cell type with subpopulations displaying distinct DNA methylation patterns. In this study, we investigated DNA methylation using reduced representation bisulfite sequencing in two CD4+ T cell populations (CD4+ memory and naïve cells) in three groups: newly diagnosed, disease modifying antirheumatic drugs (DMARD) naïve RA patients (N = 11), methotrexate (MTX) treated RA patients (N = 18), and healthy controls (N = 9) matched for age, gender and smoking status. Results: Analyses of these data revealed significantly more differentially methylated positions (DMPs) in CD4+ memory than in CD4+ naïve T cells (904 vs. 19 DMPs) in RA patients compared to controls. The majority of DMPs (72%) identified in newly diagnosed and DMARD naïve RA patients with active disease showed increased DNA methylation (39 DMPs), whereas most DMPs (80%) identified in the MTX treated RA patients in remission displayed decreased DNA methylation (694 DMPs). Interestingly, we also found that about one third of the 101 known RA risk loci overlapped (±500 kb) with the DMPs. Notably, introns of the UBASH3A gene harbor both the lead RA risk SNP and two DMPs in CD4+ memory T cells. Conclusion: Our results suggest that RA associated DNA methylation differences vary between the two T cell subsets, but are also influenced by RA characteristics such as disease activity, disease duration and/or MTX treatment.
Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome: Clinical and Radiological Considerations

Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) are relatively uncommon neurological disorders, but their detection has been increasing mainly due to clinical awareness and spreading of magnetic resonance imaging (MRI). Because these syndromes share some common clinical and radiologic features and occasionally occur in the same patient, misdiagnosis may occur. PRES is characterized by varied neurological symptoms including headache, impaired visual acuity or visual field deficit, confusion, disorders of consciousness, seizures, and motor deficits often associated to peculiar neuroradiological pattern even if uncommon localization and ischemic or hemorrhagic lesions were described. RCVS is a group of diseases typically associated with severe headaches and reversible segmental vasoconstriction of cerebral arteries, often complicated by ischemic or hemorrhagic stroke. Pathophysiological basis of PRES and RCVS are still debated but, because they share some risk factors and clinical features, a possible common origin has been supposed. Clinical course is usually self-limiting, but prognosis may fluctuate from complete recovery to death due to complications of ischemic stroke or intracranial hemorrhage. Neuroradiological techniques such as digital angiography and MRI are helpful in the diagnostic pathway and a possible prognostic role of MRI has been suggested. This review will serve to summarize clinical, neuroradiological features and controversies underlying both syndromes that may mislead the diagnostic pathway and their possible relationship with pathophysiology, clinical course, and prognosis.
c-MAF, a Swiss Army Knife for Tolerance in Lymphocytes

Beyond its well-admitted role in development and organogenesis, it is now clear that the transcription factor c-Maf has owned its place in the realm of immune-related transcription factors. Formerly introduced solely as a Th2 transcription factor, the role attributed to c-Maf has gradually broadened over the years and has extended to most, if not all, known immune cell types. The influence of c-Maf is particularly prominent among T cell subsets, where c-Maf regulates the differentiation as well as the function of multiple subsets of CD4 and CD8 T cells, lending it a crucial position in adaptive immunity and anti-tumoral responsiveness. Recent research has also revealed the role of c-Maf in controlling Th17 responses in the intestine, positioning it as an essential factor in intestinal homeostasis. This review aims to present and discuss the recent advances highlighting the particular role played by c-Maf in T lymphocyte differentiation, function, and homeostasis.
Characterization of Arabidopsis CYP79C1 and CYP79C2 by Glucosinolate Pathway Engineering in Nicotiana benthamiana Shows Substrate Specificity Toward a Range of Aliphatic and Aromatic Amino Acids

Glucosinolates (GLSs) are amino acid-derived defense compounds characteristic of the Brassicales order. Cytochromes P450s of the CYP79 family are the entry point into the biosynthetic pathway of the GLS core structure and catalyze the conversion of amino acids to oximes. In Arabidopsis thaliana, CYP79A2, CYP79B2, CYP79B3, CYP79F1, and CYP79F2 have been functionally characterized and are responsible for the biosynthesis of phenylalanine-, tryptophan-, and methionine-derived GLSs, respectively. However, the substrate(s) for CYP79C1 and CYP79C2 were unknown. Here, we investigated the function of CYP79C1 and CYP79C2 by transiently co-expressing the genes together with three sets of remaining genes required for GLS biosynthesis in Nicotiana benthamiana. Co-expression of CYP79C2 with either the aliphatic or aromatic core structure pathways resulted in the production of primarily leucine-derived 2-methylpropyl GLS and phenylalanine-derived benzyl GLS, along with minor amounts of GLSs from isoleucine, tryptophan, and tyrosine. Co-expression of CYP79C1 displayed minor amounts of GLSs from valine, leucine, isoleucine, and phenylalanine with the aliphatic core structure pathway, and similar GLS profile (except the GLS from valine) with the aromatic core structure pathway. Additionally, we co-expressed CYP79C1 and CYP79C2 with the chain elongation and aliphatic core structure pathways. With the chain elongation pathway, CYP79C2 still mainly produced 2-methylpropyl GLS derived from leucine, accompanied by GLSs derived from isoleucine and from chain-elongated mono- and dihomoleucine, but not from phenylalanine. However, co-expression of CYP79C1 only resulted in GLSs derived from chain-elongated amino acid substrates, dihomoleucine and dihomomethionine, when the chain elongation pathway was present. This shows that CYP79 activity depends on the specific pathways co-expressed and availability of amino acid precursors, and that description of GLS core structure pathways as “aliphatic” and “aromatic” pathways is not suitable, especially in an engineering context. This is the first characterization of members of the CYP79C family. Co-expression of CYP79 enzymes with engineered GLS pathways in N. benthamiana is a valuable tool for simultaneous testing of substrate specificity against multiple amino acids.
Cerebellum, Basal Ganglia, and Cortex Mediate Performance of an Aerial Pursuit Task

The affordance competition hypothesis is an ethologically inspired theory from cognitive neuroscience that provides an integrative neural account of continuous, real-time behavior, and will likely become increasingly relevant to the growing field of neuroergonomics. In the spirit of neuroergonomics in aviation, we designed a three-dimensional, first-person, continuous, and real-time fMRI task during which human subjects maneuvered a simulated airplane in pursuit of a target airplane along constantly changing headings. We introduce a pseudo-event-related, parametric fMRI analysis approach to begin testing the affordance competition hypothesis in neuroergonomic contexts, and attempt to identify regions of the brain that exhibit a linear metabolic relationship with the continuous variables of task performance and distance-from-target. In line with the affordance competition hypothesis, our results implicate the cooperation of the cerebellum, basal ganglia, and cortex in such a task, with greater involvement of the basal ganglia during good performance, and greater involvement of cortex and cerebellum during poor performance and when distance-from-target closes. We briefly review the somatic marker and dysmetria of thought hypotheses, in addition to the affordance competition hypothesis, to speculate on the intricacies of the cooperation of these brain regions in a task such as ours. In doing so, we demonstrate how the affordance competition hypothesis and other cognitive neuroscience theories are ready for testing in continuous, real-time tasks such as ours, and in other neuroergonomic settings more generally.
Pacing, Exercise Intensity, and Technique by Performance Level in Long-Distance Cross-Country Skiing

Introduction Long-distance cross-country skiing (XCS) has gained increased popularity within the past decades. However, research about long-distance XCS is limited; therefore, the aim of this study was to analyze the intensity distribution, technique application, and pacing strategies during long-distance XCS racing. Methods Heart rate (HR) and section skiing speeds of 9 elite (ranked 1–100) and 10 amateur skiers (ranked 101–1,500) during the 90-km Vasaloppet race were collected. In addition, during the first uphill, the first 1,000 skiers were video-recorded to analyze the applied skiing strategy (e.g. grip-waxed skis versus exclusive double poling). Results Mean race intensity was 82% of maximal HR and was not different between performance groups even though elite skiers skied ∼15% faster than amateurs. There was an interaction effect of section × group with a pronounced decrease in HR in amateurs compared with more even pacing in elite skiers (0.13 vs. 0.04% decrease/km) and skiing at higher percentage in the high-intensity zones in elite compared with amateurs (46 vs. 24%). Ninety-eight percent of the top 100 skiers and 59% of the first 1,000 skiers used exclusively double poling. Conclusion Elite and amateur skiers ski at comparable mean race exercise intensity, but they have clear differences in skiing speed. The difference in the pacing profiles between elite and amateur skiers (more even vs. distinct positive pacing) demonstrate the greater capacity of the former with respect to physiological capacity and highlights that amateurs seem to start too fast according to their capacities. The exclusive application of the double poling technique is no longer a phenomenon of elite skiers but is widely used among the top 1,000 ranked skiers.
ECoG Beta Suppression and Modulation During Finger Extension and Flexion

Neural oscillations originate predominantly from interacting cortical neurons and consequently reflect aspects of cortical information processing. However, their functional role is not yet fully understood and their interpretation is debatable. Amplitude modulations (AMs) in alpha (8–12 Hz), beta (13–30 Hz), and high gamma (70–150 Hz) band in invasive electrocorticogram (ECoG) and non-invasive electroencephalogram (EEG) signals change with behavior. Alpha and beta band AMs are typically suppressed (desynchronized) during motor behavior, while high gamma AMs highly correlate with the behavior. These two phenomena are successfully used for functional brain mapping and brain-computer interface (BCI) applications. Recent research found movement-phase related AMs (MPA) also in high beta/low gamma (24–40 Hz) EEG rhythms. These MPAs were found by separating the suppressed AMs into sustained and dynamic components. Sustained AM components are those with frequencies that are lower than the motor behavior. Dynamic components those with frequencies higher than the behavior. In this paper, we study ECoG beta/low gamma band (12–30 Hz/30–42 Hz) AM during repetitive finger movements addressing the question whether or not MPAs can be found in ECoG beta band. Indeed, MPA in the 12–18 Hz and 18–24 Hz band were found. This additional information may lead to further improvements in ECoG-based prediction and reconstruction of motor behavior by combining high gamma AM and beta band MPA.