Miracle-dz/UniFAR-FTUs huggingface dataset:
Interplay of m6A and H3K27 trimethylation restrains inflammation during bacterial infection

m6A controls the inflammatory response through cross-talk with H3K27me3, indicating the importance of m6A in immune homeostasis. While N6-methyladenosine (m6A) is the most prevalent modification of eukaryotic messenger RNA (mRNA) involved in various cellular responses, its role in modulating bacteria-induced inflammatory response remains elusive. Here, we showed that loss of the m6A reader YTH-domain family 2 (YTHDF2) promoted demethylation of histone H3 lysine-27 trimethylation (H3K27me3), which led to enhanced production of proinflammatory cytokines and facilitated the deposition of m6A cotranscriptionally. Mechanistically, the mRNA of lysine demethylase 6B (KDM6B) was m6A-modified and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote H3K27me3 demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis.
Vortices as Brownian particles in turbulent flows

Vortices in rotating turbulent flows move as Brownian particles with direct transition from ballistic to diffusive regimes. Brownian motion of particles in fluid is the most common form of collective behavior in physical and biological systems. Here, we demonstrate through both experiment and numerical simulation that the movement of vortices in a rotating turbulent convective flow resembles that of inertial Brownian particles, i.e., they initially move ballistically and then diffusively after certain critical time. Moreover, the transition from ballistic to diffusive behaviors is direct, as predicted by Langevin, without first going through the hydrodynamic memory regime. The transitional timescale and the diffusivity of the vortices can be collapsed excellently onto a master curve for all explored parameters. In the spatial domain, however, the vortices exhibit organized structures, as if they are performing tethered random motion. Our results imply that the convective vortices have inertia-induced memory such that their short-term movement can be predicted and their motion can be well described in the framework of Brownian motions.
Inter-kernel Reuse-aware Thread Block Scheduling

As GPUs have become more programmable, their performance and energy benefits have made them increasingly popular. However, while GPU compute units continue to improve in performance, on-chip memories lag behind and data accesses are becoming increasingly expensive in performance and energy. Emerging GPU coherence protocols can mitigate this bottleneck by exploiting data reuse in GPU caches across kernel boundaries. Unfortunately, current GPU thread block schedulers are typically not designed to expose such reuse. This article proposes new hardware thread block schedulers that optimize inter-kernel reuse while using work stealing to preserve load balance. Our schedulers are simple, decentralized, and have extremely low overhead. Compared to a baseline round-robin scheduler, the best performing scheduler reduces average execution time and energy by 19% and 11%, respectively, in regular applications, and 10% and 8%, respectively, in irregular applications.
Use of an Indoor Navigation System by Sighted and Blind Travelers

This article first reviews the pros and cons of current accessible indoor navigation systems and then describes a study using commercial smart devices to navigate routes through a complex building. Our interest was in comparing performance when using real-time narrative descriptions (system-aided condition) vs. a memory-based condition where the same narrative information was only provided to users from the route's origin. We tested two groups of blind and visually impaired (BVI) users, including people above and below 60 years of age, as well as a third sighted control group. Evaluating older BVI participants is important, as the majority of vision loss is age-related, yet navigation performance using access technology is rarely studied with this demographic. Behavioral results demonstrated that access to real-time (system-aided) information led to better navigation accuracy and greater confidence by blind users compared to the information-matched memory condition. Performance for blind participants over 60 years old was nearly identical with their younger peers—an important outcome supporting the efficacy of using navigational technologies by this fast-growing population. Route completion accuracy and requests for assistance did not reliably differ between blind and sighted participants when using the system, suggesting that access to narrative route information led to functionally equivalent navigation behavior, irrespective of visual status. Survey results revealed strong user support for real-time information and provided important guidance for future interface refinements.
Intrasound therapy: an effective alternative to sodium diclofenac phonophoresis in the management of mechanical chronic cervical spine pain

The efficacy of Sodium Diclofenac Phonophoresis (SDP) as an effective adjunct in the management of inflammation and pain has been established though its application entails complicated choices of treatment parameters. Intrasound Therapy (IST), acclaimed for its simplicity of operation has been reported to promote healing though no studies have been done on its effect in Chronic cervical spine pain (CCSP). The aim of this study was to determine if IST could be an effective therapeutic option to SDP as an adjunct in the management of CCSP. Forty seven (47) participants with CCSP that had definite diagnoses were randomly assigned into 3 groups. All participants had exercises and massage while in addition, group 1 had SDP and group 2 IST for 10 minutes each. Participants were treated for 40 minutes twice a week for 4 weeks and were evaluated for pain, Quality of life (QoL), disability and range of motion (ROM) of the cervical spine. Paired sample t -test was used to compare the outcome parameters in each group and data presented as Mean ± SEM with significance at p <0.05. IST and SDP significantly ( p ˂0.05) improved the clinical parametres compared with the control group and there were no significant ( p ˃0.05) differences in clinical outcome between the IST and SDP groups. IST was as effective as SDP and considering its relative simplicity of operation could be an alternative therapeutic adjunct in the management of chronic cervical pain. Keywords: Sodium Diclofenac Phonophoresis, Intrasound therapy, Chronic Neck pain, Neck Disability
The effects of ewe size and nutrition during pregnancy on growth and onset of puberty in female progeny

In 2005, ‘heavy’ and ‘light’ Romney ewes were selected, synchronized and artificially inseminated. Half of the ewes in each weight group were fed ad libitum and the other half were restricted to maintenance from days 21-140 of pregnancy, resulting in four groups: ‘heavy’-maintenance (HM), ‘heavy’-ad libitum (HA), ‘light’-maintenance (LM) and ‘light’-ad libitum (LA). The aim of the present study was to investigate the effects of ewe size and nutrition during pregnancy on growth and onset of puberty in female progeny. Lamb birth weights were recorded. After weaning, the progeny were managed as one flock and weighed monthly. Crayon-harnessed teaser rams were joined with the lambs to investigate the onset of puberty. Maternal nutrition during pregnancy affected live weight of lambs from 22 days of age till weaning (100 days of age) (P<0.05). During the first 22 days of life, the growth rate of lambs born to LM was lower (P<0.05) compared with the other groups (215 ± 8.2, 261 ± 8.0, 250 ± 7.9, 275 ± 7.3 grams/day, for lambs born to LM, LA, HM and HA ewes respectively). From weaning until one year of age lambs born to LM dams were lighter than lambs born to HM dams (P<0.05). No differences in the age of onset of puberty were found among the four groups. Singletons reached puberty earlier than twins (P<0.01). At 13 months of age, no long-term effect of maternal nutrition on the live weight of resulting ewe offspring was found, although dam size had a significant effect on live weight and growth rate. However, neither dam nutrition nor size had any effect on the age of onset of puberty.
Territory incognita

Tracing the lineage of territorial theorization, from legal container through dialectical, strategic and rhizomatic interpretations, this paper contends that more-than-human aspects of territory have been routinely circumvented by scholars seeking to avoid its realist, imperialist intellectual past. However, with the crisis of representation in political theory precipitated by the planetary ecological crisis, territory as a material entity has sprung alive again. This paper proposes that a reinvigorated materialist approach, informed by Deleuze and Guattari’s writings on territorial assemblages as machinic, nomadic and affective, can offer a way out of the territorial trap, reclaiming nomos from its conservative, masculine heritage.
Single-cell transcriptome analysis reveals cell lineage specification in temporal-spatial patterns in human cortical development

A single-cell survey of developing human CC was performed with comprehensive temporal and spatial information. Neurogenesis processes differ in different areas of the cortex in many species, including humans. Here, we performed single-cell transcriptome profiling of the four cortical lobes and pons during human embryonic and fetal development. We identified distinct subtypes of neural progenitor cells (NPCs) and their molecular signatures, including a group of previously unidentified transient NPCs. We specified the neurogenesis path and molecular regulations of the human deep-layer, upper-layer, and mature neurons. Neurons showed clear spatial and temporal distinctions, while glial cells of different origins showed development patterns similar to those of mice, and we captured the developmental trajectory of oligodendrocyte lineage cells until the human mid-fetal stage. Additionally, we verified region-specific characteristics of neurons in the cortex, including their distinct electrophysiological features. With systematic single-cell analysis, we decoded human neuronal development in temporal and spatial dimensions from GW7 to GW28, offering deeper insights into the molecular regulations underlying human neurogenesis and cortical development.
Aircraft observations since the 1990s reveal increases of tropospheric ozone at multiple locations across the Northern Hemisphere

Recent aircraft observations show that tropospheric ozone increased above many Northern Hemisphere regions since the mid-1990s. Tropospheric ozone is an important greenhouse gas, is detrimental to human health and crop and ecosystem productivity, and controls the oxidizing capacity of the troposphere. Because of its high spatial and temporal variability and limited observations, quantifying net tropospheric ozone changes across the Northern Hemisphere on time scales of two decades had not been possible. Here, we show, using newly available observations from an extensive commercial aircraft monitoring network, that tropospheric ozone has increased above 11 regions of the Northern Hemisphere since the mid-1990s, consistent with the OMI/MLS satellite product. The net result of shifting anthropogenic ozone precursor emissions has led to an increase of ozone and its radiative forcing above all 11 study regions of the Northern Hemisphere, despite NOx emission reductions at midlatitudes.
Bimekizumab, a Novel Humanized IgG1 Antibody That Neutralizes Both IL-17A and IL-17F

Interleukin (IL)-17A is a key driver of inflammation and the principal target of anti-IL-17 therapeutic monoclonal antibodies. IL-17A, and its structurally similar family member IL-17F, have been shown to be functionally dysregulated in certain human immune-mediated inflammatory diseases such as psoriasis, psoriatic arthritis, and axial spondyloarthritis. Given the overlapping biology of these two cytokines, we postulated that dual neutralization of IL-17A and IL-17F may provide a greater depth of clinical response in IL-17-mediated diseases than IL-17A inhibition alone. We identified 496.g1, a humanized antibody with strong affinity for IL-17A but poor affinity for IL-17F. Affinity maturation of 496.g1 to 496.g3 greatly enhanced the affinity of the Fab fragment for IL-17F while retaining strong binding to IL-17A. As an IgG1, the affinity for IL-17A and IL-17F was 3.2 pM and 23 pM, respectively. Comparison of 496.g3 IgG1 with the commercially available anti-IL-17A monoclonal antibodies ixekizumab and secukinumab, by surface plasmon resonance and in a human in vitro IL-17A functional assay, showed that 496.g3 and ixekizumab display equivalent affinity for IL-17A, and that both antibodies are markedly more potent than secukinumab. In contrast to ixekizumab and secukinumab, 496.g3 exhibited the unique feature of also being able to neutralize the biological activity of IL-17F. Therefore, antibody 496.g3 was selected for clinical development for its ability to neutralize the biologic function of both IL-17A and IL-17F and was renamed bimekizumab (formerly UCB4940). Early clinical data in patients with psoriasis, in those with psoriatic arthritis, and from the Phase 2 studies in psoriasis, psoriatic arthritis, and ankylosing spondylitis, are encouraging and support the targeted approach of dual neutralization of IL-17A and IL-17F. Taken together, these findings provide the rationale for the continued clinical evaluation of bimekizumab in patients with immune-mediated inflammatory diseases.
Comparison of Activation Patterns in Mirror Neurons and the Swallowing Network During Action Observation and Execution: A Task-Based fMRI Study

Background Observation of a goal-directed motor action can excite the respective mirror neurons, and this is the theoretical basis for action observation (AO) as a novel tool for functional recovery during stroke rehabilitation. To explore the therapeutic potential of AO for dysphagia, we conducted a task-based functional magnetic resonance imaging (fMRI) study to identify the brain areas activated during observation and execution of swallowing in healthy participants. Methods Twenty-nine healthy volunteers viewed the following stimuli during fMRI scanning: an action-video of swallowing (condition 1, defined as AO), a neutral image with a Chinese word for “watching” (condition 2), and a neutral image with a Chinese word for “swallowing” (condition 3). Action execution (AE) was defined as condition 3 minus condition 2. One-sample t-tests were performed to define the brain regions activated during AO and AE. Results Many brain regions were activated during AO, including the middle temporal gyrus, inferior frontal gyrus, pre- and postcentral gyrus, supplementary motor area, hippocampus, brainstem, and pons. AE resulted in activation of motor areas as well as other brain areas, including the inferior parietal lobule, vermis, middle frontal gyrus, and middle temporal gyrus. Two brain areas, BA6 and BA21, were activated with both AO and AE. Conclusion The left supplementary motor area (BA6) and left middle temporal gyrus (BA21), which contains mirror neurons, were activated in both AO and AE of swallowing. In this study, AO activated mirror neurons and the swallowing network in healthy participants, supporting its potential value in the treatment of dysphagia.
The Preferred Locations of Meningioma According to Different Biological Characteristics Based on Voxel-Wise Analysis

Objective: Meningiomas presented preferred intracranial distribution, which may reflect potential biological natures. This study aimed to analyze the preferred locations of meningioma according to different biological characteristics. Method: A total of 1,107 patients pathologically diagnosed with meningiomas between January 2012 and December 2016 were retrospectively analyzed. Preoperative MRI were normalized, and lesions were semiautomatically segmented. The stereospecific frequency and p value heatmaps were constructed to compare two biological phenotypes using two-tailed Fisher's exact test. Age, sex, WHO grades, extent of resection (EOR), recurrence, and immunohistochemical markers including p53, Ki67, epithelial membrane antigen (EMA), progesterone receptor (PR), and CD34 were statistically analyzed. Recurrence-free survival (RFS) were analyzed by Kaplan–Meier method. Result: Of 1,107 cases, convexity (20.8%), parasagittal (16.1%), and falx (11.4%) were the most predominant loci of meningiomas. The p-value heatmap suggested lesion predominance in the left frontal and occipital convexity among older patients while in the left sphenoid wing, and right falx, parasellar/cavernous sinus, and middle fossa among younger patients. Lesions located at anterior fossa and frontal structures were more frequently seen in the male while left parietal falx and tentorial regions, and right cerebellopontine angle in the female. Grades II and III lesions presented predominance in the frontal structures compared with grade I ones. Meningiomas at the left parasagittal sinus and falx, tentorium, intraventricular regions, and skull-base structures were significantly to receive subtotal resection. Lesions with p53 positivity were statistically located at the left frontal regions and parasellar/cavernous sinus, higher Ki67 index at the left frontal and bilateral parietal convexity and right parasellar/cavernous sinus, EMA negativity at the right olfactory groove and left middle fossa, and CD34 positivity at the sellar regions and right sphenoid wing. Tumor recurrence rates for grades I, II, and III were 2.8, 7.9, and 53.8%, respectively. Inferior RFS, higher Ki67 index, grades II and III, and a larger preoperative volume were observed in older patients. Recurrent meningiomas were more frequently found at the occipital convexity, tentorium, sellar regions, parasagittal sinus, and left sphenoid wing. Conclusion: The preferred locations of meningioma could be observed according to different biological characteristics, which might be helpful for clinical decisions.
Identification of the Prognostic Value of Immune-Related Genes in Esophageal Cancer

Esophageal cancer (EC) is a serious malignant tumor, both in terms of mortality and prognosis, and immune-related genes (IRGs) are key contributors to its development. In recent years, immunotherapy for tumors has been widely studied, but a practical prognostic model based on immune-related genes (IRGs) in EC has not been established and reported. This study aimed to develop an immunogenomic risk score for predicting survival outcomes among EC patients. In this study, we downloaded the transcriptome profiling data and matched clinical data of EC patients from The Cancer Genome Atlas (TCGA) database and found 4,094 differentially expressed genes (DEGs) between EC and normal esophageal tissue (p < 0.05 and fold change >2). Then, the intersection of DEGs and the immune genes in the “ImmPort” database resulted in 303 differentially expressed immune-related genes (DEIRGs). Next, through univariate Cox regression analysis of DEIRGs, we obtained 17 immune genes related to prognosis. We detected nine optimal survival-associated IRGs (HSPA6, CACYBP, DKK1, EGF, FGF19, GAST, OSM, ANGPTL3, NR2F2) by using Lasso regression and multivariate Cox regression analyses. Finally, we used those survival-associated IRGs to construct a risk model to predict the prognosis of EC patients. This model could accurately predict overall survival in EC and could be used as a classifier for the evaluation of low-risk and high-risk groups. In conclusion, we identified a practical and robust nine-gene prognostic model based on immune gene dataset. These genes may provide valuable biomarkers and prognostic predictors for EC patients and could be further studied to help understand the mechanism of EC occurrence and development.
Nondual Awareness and Minimal Phenomenal Experience

Minimal phenomenal experiences (MPEs) have recently gained attention in the fields of neuroscience and philosophy of mind. They can be thought of as episodes of greatly reduced or even absent phenomenal content together with a reduced level of arousal. It has also been proposed that MPEs are cases of consciousness-as-such. Here, we present a different perspective, that consciousness-as-such is first and foremost a type of awareness, that is, non-conceptual, non-propositional, and nondual, in other words, non-representational. This awareness is a unique kind and cannot be adequately specified by the two-dimensional model of consciousness as the arousal level plus the phenomenal content or by their mental representations. Thus, we suggest that to understand consciousness-as-such, and by extension consciousness in general, more accurately, we need to research it as a unique kind.
NLRP3 Is Involved in the Maintenance of Cerebral Pericytes

Pericytes play a central role in regulating the structure and function of capillaries in the brain. However, molecular mechanisms that drive pericyte proliferation and differentiation are unclear. In our study, we immunostained NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-deficient and wild-type littermate mice and observed that NLRP3 deficiency reduced platelet-derived growth factor receptor β (PDGFRβ)-positive pericytes and collagen type IV immunoreactive vasculature in the brain. In Western blot analysis, PDGFRβ and CD13 proteins in isolated cerebral microvessels from the NLRP3-deficient mouse brain were decreased. We further treated cultured pericytes with NLRP3 inhibitor, MCC950, and demonstrated that NLRP3 inhibition attenuated cell proliferation but did not induce apoptosis. NLRP3 inhibition also decreased protein levels of PDGFRβ and CD13 in cultured pericytes. On the contrary, treatments with IL-1β, the major product of NLRP3-contained inflammasome, increased protein levels of PDGFRβ, and CD13 in cultured cells. The alteration of PDGFRβ and CD13 protein levels were correlated with the phosphorylation of AKT. Inhibition of AKT reduced both protein markers and abolished the effect of IL-1β activation in cultured pericytes. Thus, NLRP3 activation might be essential to maintain pericytes in the healthy brain through phosphorylating AKT. The potential adverse effects on the cerebral vascular pericytes should be considered in clinical therapies with NLRP3 inhibitors.
Do you Play or Do you Train? Insights From Individual Sports for Training Load and Injury Risk Management in Team Sports Based on Individualization

Citation: Boullosa D, Casado A, Claudino JG, Jiménez-Reyes P, Ravé G, Castaño-Zambudio A, Lima-Alves A, de Oliveira SA Jr, Dupont G, Granacher U and Zouhal H (2020) Do you Play or Do you Train? Insights From Individual Sports for Training Load and Injury Risk Management in Team Sports Based on Individualization. Front. Physiol. 11:995. doi: 10.3389/fphys.2020. 00995 Do you Play or Do you Train? Insights From Individual Sports for Training Load and Injury Risk Management in Team Sports Based on Individualization