Miracle-dz/UniFAR-FTUs huggingface dataset:
Prostaglandin E2 promotes embryonic vascular development and maturation in zebrafish

ABSTRACT Prostaglandin (PG)-E2 is essential for growth and development of vertebrates. PGE2 binds to G-coupled receptors to regulate embryonic stem cell differentiation and maintains tissue homeostasis. Overproduction of PGE2 by breast tumor cells promotes aggressive breast cancer phenotypes and tumor-associated lymphangiogenesis. In this study, we investigated novel roles of PGE2 in early embryonic vascular development and maturation with the microinjection of PGE2 in fertilized zebrafish (Danio rerio) eggs. We injected Texas Red dextran to trace vascular development. Embryos injected with the solvent of PGE2 served as vehicle. Distinct developmental changes were noted from 28–96 h post fertilization (hpf), showing an increase in embryonic tail flicks, pigmentation, growth, hatching and larval movement post-hatching in the PGE2-injected group compared to the vehicle. We recorded a significant increase in trunk vascular fluorescence and maturation of vascular anatomy, embryo heartbeat and blood vessel formation in the PGE2 injected group. At 96 hpf, all larvae were euthanized to measure vascular marker mRNA expression. We observed a significant increase in the expression of stem cell markers efnb2a, ephb4a, angiogenesis markers vegfa, kdrl, etv2 and lymphangiogenesis marker prox1 in the PGE2-group compared to the vehicle. This study shows the novel roles of PGE2 in promoting embryonic vascular maturation and angiogenesis in zebrafish. This article has an associated First Person interview with the first author of the paper. Summary: Overproduction of PGE2 causes inflammation and cancer and its blockage results in serious physiological consequences. This study investigated the novel roles of PGE2 in early vascular development of zebrafish.
The GalNAc-T Activation (GALA) Pathway: Drivers and markers

The enzymes GALNTs add GalNAc sugar to Ser and Thr residues, forming the Tn glycan. GALNTs are activated by trafficking from Golgi to ER, a process driven by the Src kinase and negatively regulated by ERK8. This GALNTs activation (aka GALA) pathway induces high Tn levels and is a key driver of liver tumor growth. Recently, Tabak and colleagues have contested our previous data that EGF stimulation can induce GALNTs relocation. Here, we show that relocation induced by EGF is actually detectable in the images acquired by Tabak et al. Furthermore, we show that expression of EGFR enhances relocation and appears required to drive relocation induced by ERK8 depletion. We also propose that quantification of O-glycosylation of the ER resident protein PDIA4 provides an alternative measure of GALA. In sum, we demonstrate that non-reproducibility was due to experimental errors, that EGFR is indeed a driver of GALA and propose additional markers to facilitate the study of this pathway.
Smart Camera Aware Crowd Counting via Multiple Task Fractional Stride Deep Learning †

Estimating the number of people in highly clustered crowd scenes is an extremely challenging task on account of serious occlusion and non-uniformity distribution in one crowd image. Traditional works on crowd counting take advantage of different CNN like networks to regress crowd density map, and further predict the count. In contrast, we investigate a simple but valid deep learning model that concentrates on accurately predicting the density map and simultaneously training a density level classifier to relax parameters of the network to prevent dangerous stampede with a smart camera. First, a combination of atrous and fractional stride convolutional neural network (CAFN) is proposed to deliver larger receptive fields and reduce the loss of details during down-sampling by using dilated kernels. Second, the expanded architecture is offered to not only precisely regress the density map, but also classify the density level of the crowd in the meantime (MTCAFN, multiple tasks CAFN for both regression and classification). Third, experimental results demonstrated on four datasets (Shanghai Tech A (MAE = 88.1) and B (MAE = 18.8), WorldExpo’10(average MAE = 8.2), NS UCF_CC_50(MAE = 303.2) prove our proposed method can deliver effective performance.
Echoing the emotions of others: empathy is related to how adults and children map emotion onto the body

ABSTRACT Empathy involves a mapping between the emotions observed in others and those experienced in one’s self. However, effective social functioning also requires an ability to differentiate one’s own emotional state from that of others. Here, we sought to examine the relationship between trait measures of empathy and the self-other distinction during emotional experience in both children and adults. We used a topographical self-report method (emBODY tool) in which participants drew on a silhouette of a human body where they felt an emotional response while watching film and music clips, as well as where they believed the character in the film or performer was feeling an emotion. We then assessed how the degree of overlap between the bodily representation of self versus other emotions related to trait empathy. In adults, the degree of overlap in the body maps was correlated with Perspective Taking. This relationship between cognitive empathy and degree of overlap between self and other was also found with children (8–11 years old), even though children performed worse on the task overall. The results suggest that mapping emotions observed or imagined in other’s bodies onto our own is related to the development of empathy.
Chiral Inversion of Thiolate-Protected Gold Nanoclusters via Core Reconstruction without Breaking a Au–S Bond

On the basis of density functional theory computations of the well-known chiral Au38(SR)24 nanocluster and its Pd- and Ag-doped derivatives, we propose here a mechanism for chiral inversion that does not require the breaking of a metal–sulfur bond at the metal–ligand interface but features a collective rotation of the gold core. The calculated energy barriers for this mechanism for Au38 and Pd-doped Au38 are in the range of 1–1.5 eV, significantly lower than barriers involving the breakage of Au–S bonds (2.5 eV). For Ag-doped Au38, barriers for both mechanisms are similar (1.3–1.5 eV). Inversion barriers for a larger chiral Au144(SR)60 are much higher (2.5−2.8 eV). Our computed barriers are in good agreement with racemization barriers estimated from existing experiments for bare and doped Au38. These results highlight the sensitivity of chiral inversion to the size, structure, and metal composition of the metal core and sensitivity to the detailed structure of the metal–thiolate interface. Our work also predicts that enantiopure Au144(SR)60 clusters would be promising materials for applications requiring high resistance to chiral inversion.
A systematic literature review and meta-analysis of minimal residual disease as a prognostic indicator in adult B-cell acute lymphoblastic leukemia

Minimal (or ‘measurable’) residual disease in acute lymphoblastic leukemia appears to be a prognostic indicator, with potential value in informing individualized treatment decisions. Complete understanding of the strength of the association between minimal residual disease and long-term outcomes is, however, lacking. A systematic literature review and meta-analysis were performed to elucidate the clinical significance of minimal residual disease with respect to relapse-free survival and overall survival in precursor B-cell acute lymphoblastic leukemia. A total of 23 articles and abstracts, most published between 2012 and 2016, were identified for inclusion in the primary meta-analysis. Typically, patients were in their first complete remission at the time of minimal residual disease assessment; in two studies, all patients were in their second, or later, complete remission. The primary analysis revealed improved relapse-free survival across all studies for patients who achieved minimal residual disease negativity (random effects hazard ratio, 2.34; 95% confidence interval, 1.91–2.86). Improved overall survival for patients who achieved minimal residual disease negativity was also observed (hazard ratio, 2.19; 95% confidence interval, 1.63–2.94). There was no observed difference in the impact of minimal residual disease status in subgroups based on disease stage, minimal residual disease sensitivity threshold level, Philadelphia chromosome status, histological phenotype, risk group, minimal residual disease testing location, minimal residual disease timing after induction, or minimal residual disease detection method. Despite heterogeneity in study design and patient populations between the contributing studies, these data provide a compelling argument for minimal residual disease as a clinical tool for assessing prognosis and guiding treatment decisions in precursor B-cell acute lymphoblastic leukemia.
Reaction Time Improvements by Neural Bistability

The often reported reduction of Reaction Time (RT) by Vision Training) is successfully replicated by 81 athletes across sports. This enabled us to achieve a mean reduction of RTs for athletes eye-hand coordination of more than 10%, with high statistical significance. We explain how such an observed effect of Sensorimotor systems’ plasticity causing reduced RT can last in practice for multiple days and even weeks in subjects, via a proof of principle. Its mathematical neural model can be forced outside a previous stable (but long) RT into a state leading to reduced eye-hand coordination RT, which is, again, in a stable neural state.
Interactions between plant genome size, nutrients and herbivory by rabbits, molluscs and insects on a temperate grassland

Angiosperm genome sizes (GS) vary ca 2400-fold. Recent research has shown that GS influences plant abundance, and plant competition. There are also tantalizing reports that herbivores may select plants as food dependent on their GS. To test the hypothesis that GS plays a role in shaping plant communities under herbivore pressure, we exploit a grassland experiment that has experimentally excluded herbivores and applied nutrient over 8 years. Using phylogenetically informed statistical models and path analyses, we show that under rabbit grazing, plant species with small GS generated the most biomass. By contrast, on mollusc and insect-grazed plots, it was the plant species with larger GS that increased in biomass. GS was also shown to influence plant community properties (e.g. competitive strategy, total biomass) although the impact varied between different herbivore guilds (i.e. rabbits versus invertebrates) and nutrient inputs. Overall, we demonstrate that GS plays a role in influencing plant–herbivore interactions, and suggest potential reasons for this response, which include the impact of GS on a plant's response to different herbivore guilds, and on a plant's nutrient quality. The inclusion of GS in ecological models has the potential to expand our understanding of plant productivity and community ecology under nutrient and herbivore stress.
The Amino Acid Permease 5 (OsAAP5) Regulates Tiller Number and Grain Yield in Rice1

OsAAP5 might mediate basic amino acids (Lys and Arg) and neutral amino acids (Val and Ala) transport to affect cytokinin pathway. As fundamental nutrients, amino acids are important for rice (Oryza sativa) growth and development. Here, we identified the amino acid permease 5 (OsAAP5), that regulates tiller number and grain yield in rice. The OsAAP5 promoter sequence differed between indica and japonica rice varieties. Lower expression of OsAAP5 in the young leaf blade in indica varieties than in japonica varieties was associated with more tillers in indica than in japonica. Down-regulation of OsAAP5 expression in japonica using RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats led to increases in tiller number and grain yield, whereas OsAAP5 overexpression (OE) had the opposite effect. Both a protoplast amino acid uptake assay and HPLC analysis indicated that more basic (Lys, Arg) and neutral (Val, Ala) amino acids were transported and accumulated in the OE lines than in the wild type, but the opposite was observed in the RNAi lines. Furthermore, exogenous application of Lys, Arg, Val, and Ala in the OE lines substantially inhibited tiller bud elongation, but the effect was lost in the RNAi lines. Notably, concentrations of the cytokinins cis-zeatin and dihydrozeatin were much lower in the OE lines than in the wild type, whereas concentrations in the RNAi lines were higher. Thus, OsAAP5 could regulate tiller bud outgrowth by affecting cytokinin levels, and knockout of OsAAP5 could be valuable for japonica breeding programs seeking high yield and grain quality.
A Deep Learning Framework for Driving Behavior Identification on In-Vehicle CAN-BUS Sensor Data

Human driving behaviors are personalized and unique, and the automobile fingerprint of drivers could be helpful to automatically identify different driving behaviors and further be applied in fields such as auto-theft systems. Current research suggests that in-vehicle Controller Area Network-BUS (CAN-BUS) data can be used as an effective representation of driving behavior for recognizing different drivers. However, it is difficult to capture complex temporal features of driving behaviors in traditional methods. This paper proposes an end-to-end deep learning framework by fusing convolutional neural networks and recurrent neural networks with an attention mechanism, which is more suitable for time series CAN-BUS sensor data. The proposed method can automatically learn features of driving behaviors and model temporal features without professional knowledge in features modeling. Moreover, the method can capture salient structure features of high-dimensional sensor data and explore the correlations among multi-sensor data for rich feature representations of driving behaviors. Experimental results show that the proposed framework performs well in the real world driving behavior identification task, outperforming the state-of-the-art methods.
T Cells Specific for an Unconventional Natural Antigen Fail to Recognize Leukemic Cells

MHC-bound peptides derived from aberrant proteins may be an immunotherapeutic target on cancer cells. However, T cells recognizing such an antigen failed to react against leukemic cells. Thus, concern is warranted for immunotherapies targeting such antigens. MHC-bound peptides from aberrant proteins may be a specific immunotherapeutic target on cancer cells. Because of difficulties in identifying such antigens, viral or model antigens have so far been used to study their biological relevance. We here identify a naturally existing human T-cell epitope derived from a truncated protein. The antigenic peptide is derived from the gene TTK only through an alternative transcript containing a premature termination codon that may target the transcript for nonsense-mediated decay (NMD). This antigen is recognized by HLA-A*02:01–restricted CD8+ T cells derived from an allotransplanted leukemia patient. Functional analyses showed that these T cells failed to recognize several HLA-matched primary leukemic cells that expressed the alternative TTK transcript. Conventional antigen processing and presentation were not affected, suggesting that leukemic cells modify the generation of antigens processed from aberrant proteins. This natural TTK epitope provides insights in the source of transcripts producing antigenic epitopes in healthy and leukemic cells. Our data underscore potential pitfalls of targeting NMD-derived or other unconventionally generated epitopes as immunotherapeutic approach.
A risk–benefit assessment strategy to exclude cervical artery dissection in spinal manual-therapy: a comprehensive review

Abstract Cervical artery dissection refers to a tear in the internal carotid or the vertebral artery that results in an intramural haematoma and/or an aneurysmal dilatation. Although cervical artery dissection is thought to occur spontaneously, physical trauma to the neck, especially hyperextension and rotation, has been reported as a trigger. Headache and/or neck pain is the most common initial symptom of cervical artery dissection. Other symptoms include Horner’s syndrome and lower cranial nerve palsy. Both headache and/or neck pain are common symptoms and leading causes of disability, while cervical artery dissection is rare. Patients often consult their general practitioner for headache and/or neck pain, and because manual-therapy interventions can alleviate headache and/or neck pain, many patients seek manual therapists, such as chiropractors and physiotherapists. Cervical mobilization and manipulation are two interventions that manual therapists use. Both interventions have been suspected of being able to trigger cervical artery dissection as an adverse event. The aim of this review is to provide an updated step-by-step risk–benefit assessment strategy regarding manual therapy and to provide tools for clinicians to exclude cervical artery dissection. Key messages Cervical mobilization and/or manipulation have been suspected to be able to trigger cervical artery dissection (CAD). However, these assumptions are based on case studies which are unable to established direct causality. The concern relates to the chicken and the egg discussion, i.e. whether the CAD symptoms lead the patient to seek cervical manual-therapy or whether the cervical manual-therapy provoked CAD along with the non-CAD presenting complaint. Thus, instead of proving a nearly impossible causality hypothesis, this study provide clinicians with an updated step-by-step risk–benefit assessment strategy tool to (a) facilitate clinicians understanding of CAD, (b) appraise the risk and applicability of cervical manual-therapy, and (c) provide clinicians with adequate tools to better detect and exclude CAD in clinical settings.
Identification and sequence characterization of melanocortin 1 receptor gene (MC1R) in Bos indicus versus (Bos taurus X Bos indicus)

Abstract Melanocortin 1 receptor (MC1R) plays a vital role in melanogenesis and determines coat color of mammals. Polymorphic variants in MC1R, causing coat color variation, were described in few mammals; however, such studies were not done in cattle. The objective of the study was to explore the association of MC1R gene polymorphism within Tharparkar (Bos indicus) and Karan Fries (B. indicus X Bos taurus) cattle. Genomic DNA isolated from blood samples of Tharparkar breed by modified Phenol: Chloroform; Isoamyl alcohol method. Using genomic DNA as template for PCR, MC1R gene was amplified and sequenced. The sequences were analyzed and submitted to Genbank with Acc.No MG373615-MG373644. Comparison of sequence alignment with other bovine species using ClustalW revealed 99–96% similarity. MC1R gene phylogenetic analyses were analyzed using MEGA X. The MC1R gene tree, protein domains and genetic variation of cattle were retrieved from Ensemble Asia Cattle Genome Browser. Eight single nucleotide polymorphisms (SNPs) (c.296T > C, c.583T > C, c.663C > T, c.830T > C, c.853G > A, c.880G > A, c.906C > G, c.927C > T) in CDS reveal high genetic variability. Subsequent to amino acid changes p.L99P, p.F195L, p.F277S, p.A285T and p.D293N, p.R302S, respectively found in seven-transmembrane. Mutations appeared in MC1R of B. taurus with white and black coat color as compared to B. indicus with white coat. GRAPHICAL ABSTRACT
Cellular retinoic acid binding protein-II expression and its potential role in skin aging

Skin aging is an intricate biological process consisting of intrinsic and extrinsic alterations of epidermal and dermal structures. Retinoids play an important role in epidermal cell growth and differentiation and are beneficial to counteract skin aging. Cellular retinoic acid binding protein-II (CRABP-II) selectively binds all trans-retinoic acid, the most active retinoid metabolite, contributing to regulate intracytoplasmic retinoid trafficking and keratinocyte differentiation. Immunohistochemistry revealed a reduced epidermal and dermal CRABP-II expression in aged human and mouse skin. To better clarify the role of CRABP-II, we investigated age-related skin changes in CRABP-II knock-out mice. We documented an early reduction of keratinocyte layers, proliferation and differentiation rate, dermal and hypodermal thickness, pilosebaceous units and dermal vascularity in CRABP-II knock-out compared with wild-type mice. Ultrastructural investigation documented reduced number and secretion of epidermal lamellar bodies in CRABP-II knock-out compared with wild-type mice. Cultured CRABP-II knock-out-derived dermal fibroblasts proliferated less and showed reduced levels of TGF-β signal-related genes, Col1A1, Col1A2, and increased MMP2 transcripts compared with those from wild-type. Our data strongly support the hypothesis that a reduction of CRABP-II expression accelerates and promotes skin aging, and suggest CRABP-II as a novel target to improve the efficacy of retinoid-mediated anti-aging therapies.
Combined Deep Brain Stimulation of Subthalamic Nucleus and Ventral Intermediate Thalamic Nucleus in Tremor‐Dominant Parkinson's Disease Using a Parietal Approach

Despite its efficacy in tremor‐suppression, the ventral intermediate thalamic (VIM) nucleus has largely been neglected in deep brain stimulation (DBS) for tremor‐dominant Parkinson's disease (tdPD). The employment of a parietal approach, however, allows stimulation of VIM and subthalamic nucleus (STN) using one trajectory only and thus constitutes a promising alternative to existing strategies. In the present study, we investigate safety and efficacy of combined lead implantation and stimulation of STN and VIM using a parietal approach.
Relationship between the earlobe crease and brain white matter abnormalities in apparently healthy subjects*

Background/aim In the present study we aimed to investigate whether the earlobe crease (ELC) might provide predictive information about white matter intensities (WMIs) in the brain that reflect brain aging. Materials and methods A total of 350 individuals examined from January 2016 to July 2016 were screened. Patients with known demyelinating white matter disease, neurodegenerative disorders, cerebrovascular event history, or brain tumors were excluded from the study. Finally, 285 cases were included in the study. The four-point cerebral intensity classification system of Fazekas was used in the evaluation of the brain. The ELC was evaluated by inspection. Results A total of 285 patients were enrolled consecutively. The incidence of WMI was significantly higher in patients with ELC than the others. Age (95% CI: 1.105–1.213, P < 0.001) and ELC (95% CI: 0.098–0.783, P = 0.015) were found as an independent determinants of abnormal WMI. ELC predicted abnormal WMIs with 89% specificity and 62% sensitivity. Conclusion The presence of an ELC may provide predictive information in terms of detecting abnormal WMIs with prognostic impact in apparently healthy subjects.