Miracle-dz/UniFAR-FTUs huggingface dataset:
Pim1 Kinase Inhibitors Exert Anti-Cancer Activity Against HER2-Positive Breast Cancer Cells Through Downregulation of HER2

The proviral integration site for moloney murine leukemia virus 1 (Pim1) is a serine/threonine kinase and able to promote cell proliferation, survival and drug resistance. Overexpression of Pim1 has been observed in many cancer types and is associated with the poor prognosis of breast cancer. However, it remains unclear whether Pim1 kinase is a potential therapeutic target for breast cancer patients. In this study, we found that Pim1 expression was strongly associated with HER2 expression and that HER2-overexpressing breast cancer cells were more sensitive to Pim1 inhibitor-induced inhibitions of cell viability and metastatic ability. Mechanistically, Pim1 inhibitor suppressed the expression of HER2 at least in part through transcriptional level. More importantly, Pim1 inhibitor overcame the resistance of breast cancer cells to HER2 tyrosine kinase inhibitor lapatinib. In summary, downregulation of HER2 by targeting Pim1 may be a promising and effective therapeutic approach not only for anti-cancer growth but also for circumventing lapatinib resistance in HER2-positive breast cancer patients.
Evaluation of Head Injury Criteria for Injury Prediction Effectiveness: Computational Reconstruction of Real-World Vulnerable Road User Impact Accidents

This study evaluates the effectiveness of various widely used head injury criteria (HICs) in predicting vulnerable road user (VRU) head injuries due to road traffic accidents. Thirty-one real-world car-to-VRU impact accident cases with detailed head injury records were collected and replicated through the computational biomechanics method; head injuries observed in the analyzed accidents were reconstructed by using a finite element (FE)-multibody (MB) coupled pedestrian model [including the Total Human Model for Safety (THUMS) head–neck FE model and the remaining body segments of TNO MB pedestrian model], which was developed and validated in our previous study. Various typical HICs were used to predict head injuries in all accident cases. Pearson’s correlation coefficient analysis method was adopted to investigate the correlation between head kinematics-based injury criteria and the actual head injury of VRU; the effectiveness of brain deformation-based injury criteria in predicting typical brain injuries [such as diffuse axonal injury diffuse axonal injury (DAI) and contusion] was assessed by using head injury risk curves reported in the literature. Results showed that for head kinematics-based injury criteria, the most widely used HICs and head impact power (HIP) can accurately and effectively predict head injury, whereas for brain deformation-based injury criteria, the maximum principal strain (MPS) behaves better than cumulative strain damage measure (CSDM0.15 and CSDM0.25) in predicting the possibility of DAI. In comparison with the dilatation damage measure (DDM), MPS seems to better predict the risk of brain contusion.
Comparative Transcriptome and DNA Methylation Analysis of Phenotypic Plasticity in the Pacific Abalone (Haliotis discus hannai)

Phenotypic plasticity is an adaptive mechanism used by organisms to cope with environmental fluctuations. Pacific abalone (Haliotis discus hannai) are large-scale farmed in the temperate area of northern China and in the warmer waters of southern China. RNA-seq and comparative transcriptomic analysis here were performed to determine if the northern and southern populations have evolved divergent plasticity and if functional differences are associated with protein synthesis and growth-related biological progress. The DNA methylation (5mC) landscape of H. discus hannai from the two populations using whole genomic bisulfite sequencing (WGBS), exhibited different epigenetic patterns. The southern population had significant genomic hypo-methylation that may have resulted from long-term acclimation to heat stress. Combining 790 differentially expressed genes (DEGs) and 7635 differentially methylated genes (DMGs), we found that methylation within the gene body might be important in predicting abalone gene expression. Genes related to growth, development, transduction, and apoptosis may be regulated by methylation and could explain the phenotypic divergence of H. discus hannai. Our findings not only emphasize the significant roles of adaptive plasticity in the acclimation of H. discus hannai to high temperatures but also provide a new understanding of the epigenetic mechanism underlying the phenotypic plasticity in adaptation to climate change for marine organisms.
Neoliberal Ideology in France: A Qualitative Inquiry

This article adds to the existing literature on neoliberal ideology by investigating its content and contours in a context historically marked by statism. Very few studies in social psychology have looked at how neoliberal ideology transpires out of people's discourses and none have done so in such contexts. Yet, this appears necessary in order to better understand its actual influence and how it interacts with localized norms. Relying on a qualitative analysis of 32 semi-structured interviews and on the existing literature, we identified five central themes of neoliberal ideology in France: State prerogatives, competition, abstraction from institutional and social contexts, the entrepreneurial self and emotional management. Results suggest that the influence of neoliberal ideology transpires in the way people envision competition as something natural and motivating, in the way they distance themselves from their immediate and distant contexts, and in the way they value and engage in self-regulation while pursuing happiness and self-optimization. We also found that, in the French context, neoliberal ideology was not necessarily associated to the willingness to see the State step back and to the rationalization of all types of inequalities. Indeed, in the eyes of participants, the State largely remains the guarantor of public services and should ensure an equality of opportunity. This study highlights the value of relying on a qualitative approach to provide a rich and complex account of social realities such as ideologies.
Common Variants in NUS1 and GP2 Genes Contributed to the Risk of Gestational Diabetes Mellitus

Background Recently, NUS1 and GP2 genes were reported to be associated with the risk of type 2 diabetes (T2D) in a Japanese population. Given the sharing of pathogenic contribution from genetic factors between T2D and gestational diabetes mellitus (GDM), we conducted the study to systematically examine the relationship of NUS1 and GP2 genes with the susceptibility to GDM in Chinese Han population. Methods A total of 4,250 subjects comprised of 1,282 patients with GDM and 2,968 controls were recruited, and 20 tag single nucleotide polymorphisms (SNPs) (10 from NUS1 and 10 from GP2) were selected for genotyping. Association analyses were conducted for GDM and its related biomedical indexes including fasting glucose and HbA1c levels. Results Two SNPs, rs80196932 from NUS1 (P=2.93×10-5) and rs117267808 from GP2 (P=5.68×10-5), were identified to be significantly associated with the risk of GDM. Additionally, SNP rs80196932 was significantly associated with HbA1c level in both patients with GDM (P=0.0009) and controls (P=0.0003), while SNP rs117267808 was significantly associated with fasting glucose level in both patients with GDM (P=0.0008) and controls (P=0.0007). Serum levels of protein NUS1 and GP2 were measured for the study subjects, and significant differences were identified among groups with different genotypes of SNP rs80196932 and rs117267808, respectively. Conclusions Our findings indicate that NUS1 and GP2 genes contribute to the risk of GDM, which would help to offer the potential to improve our understanding of the etiology of GDM and, in turn, could facilitate the development of novel medicines and treatments for GDM.
Genome-Wide Association Mapping of bc-1 and bc-u Reveals Candidate Genes and New Adjustments to the Host-Pathogen Interaction for Resistance to Bean Common Mosaic Necrosis Virus in Common Bean

Bean common mosaic necrosis virus (BCMNV) is a major disease in common bean (Phaseolus vulgaris L.). Host plant resistance is the primary disease control. We sought to identify candidate genes to better understand the host-pathogen interaction and develop tools for marker-assisted selection (MAS). A genome-wide association study (GWAS) approach using 182 lines from a race Durango Diversity Panel (DDP) challenged by BCMNV isolates NL-8 [Pathogroup (PG)-III] and NL-3 (PG-VI), and genotyped with 1.26 million single-nucleotide polymorphisms (SNPs), revealed significant peak regions on chromosomes Pv03 and Pv05, which correspond to bc-1 and bc-u resistance gene loci, respectively. Three candidate genes were identified for NL-3 and NL-8 resistance. Side-by-side receptor-like protein kinases (RLKs), Phvul.003G038700 and Phvul.003G038800 were candidate genes for bc-1. These RLKs were orthologous to linked RLKs associated with virus resistance in soybean (Glycine max). A basic Leucine Zipper (bZIP) transcription factor protein is the candidate gene for bc-u. bZIP protein gene Phvul.005G124100 carries a unique non-synonymous mutation at codon 14 in the first exon (Pv05: 36,114,516 bases), resulting in a premature termination codon that causes a nonfunctional protein. SNP markers for bc-1 and bc-u and new markers for I and bc-3 genes were used to genotype the resistance genes underpinning BCMNV phenotypes in the DDP, host group (HG) differentials, and segregating F3 families. Results revealed major adjustments to the current host-pathogen interaction model: (i) there is only one resistance allele bc-1 for the Bc-1 locus, and differential expression of the allele is based on presence vs. absence of bc-u; (ii) bc-1 exhibits dominance and incomplete dominance; (iii) bc-1 alone confers resistance to NL-8; (iv) bc-u was absent from HGs 2, 4, 5, and 7 necessitating a new gene symbol bc-ud to reflect this change; (v) bc-ud alone delays susceptible symptoms, and when combined with bc-1 enhanced resistance to NL-3; and (vi) bc-ud is on Pv05, not Pv03 as previously thought. These candidate genes, markers, and adjustments to the host-pathogen interaction will facilitate breeding for resistance to BCMNV and related Bean common mosaic virus (BCMV) in common bean.
Combined Biosynthetic Pathway Engineering and Storage Pool Expansion for High-Level Production of Ergosterol in Industrial Saccharomyces cerevisiae

Ergosterol, a terpenoid compound produced by fungi, is an economically important metabolite serving as the direct precursor of steroid drugs. Herein, ergsosterol biosynthetic pathway modification combined with storage capacity enhancement was proposed to synergistically improve the production of ergosterol in Saccharomyces cerevisiae. S. cerevisiae strain S1 accumulated the highest amount of ergosterol [7.8 mg/g dry cell weight (DCW)] among the wild-type yeast strains tested and was first selected as the host for subsequent metabolic engineering studies. Then, the push and pull of ergosterol biosynthesis were engineered to increase the metabolic flux, overexpression of the sterol acyltransferase gene ARE2 increased ergosterol content to 10 mg/g DCW and additional overexpression of a global regulatory factor allele (UPC2-1) increased the ergosterol content to 16.7 mg/g DCW. Furthermore, considering the hydrophobicity sterol esters and accumulation in lipid droplets, the fatty acid biosynthetic pathway was enhanced to expand the storage pool for ergosterol. Overexpression of ACC1 coding for the acetyl-CoA carboxylase increased ergosterol content from 16.7 to 20.7 mg/g DCW. To address growth inhibition resulted from premature accumulation of ergosterol, auto-inducible promoters were employed to dynamically control the expression of ARE2, UPC2-1, and ACC1. Consequently, better cell growth led to an increase of ergosterol content to 40.6 mg/g DCW, which is 4.2-fold higher than that of the starting strain. Finally, a two-stage feeding strategy was employed for high-density cell fermentation, with an ergosterol yield of 2986.7 mg/L and content of 29.5 mg/g DCW. This study provided an effective approach for the production of ergosterol and other related terpenoid molecules.
Expression and Function Analysis of Interleukin-17A/F1, 2, and 3 Genes in Yellow Catfish (Pelteobagrus fulvidraco): Distinct Bioactivity of Recombinant IL-17A/F1, 2, and 3

In mammals, Interleukin-17 cytokine family plays critical roles in both acute and chronic inflammatory responses. In fish species, three Interleukin-17A/F (IL-17A/F) genes have been identified to be homologous to mammalian IL-17A and IL-17F, but little is known about their functional activity. In this study, Pf_IL-17A/F1, 2 and 3 genes were cloned from yellow catfish (Pelteobagrus fulvidraco) and they differed in protein structure and exon length, implying that they may have divergent bioactivity. Real-time quantitative PCR analyses revealed that three Pf_IL-17A/F genes were highly expressed in blood and mucosal tissues (skin+mucus and gill) from healthy adult fish. The mRNA expressions of Pf_IL-17A/F1, 2 and 3 genes were significantly up-regulated in the gill, skin+mucus, head kidney and spleen after challenge with Edwardsiella ictaluri and in the isolated peripheral blood leucocytes (PBLs) of yellow catfish after stimulation with phytohaemagglutinin (PHA), lipopolysaccharides (LPS), peptidoglycan (PGN) and polyinosinic-polycytidylic acid (Poly I:C). These results indicate that Pf_IL-17A/F1, 2 and 3 genes may play a vital role in the regulation of immune against pathogens. Additionally, the recombinant (r) Pf_IL-17A/F1, 2 and 3 proteins significantly induced the mRNA expressions of proinflammatory cytokines, chemokines and antibacterial peptides genes, and the rPf_IL-17A/F 2 and 3 proteins promoted phagocytosis of PBLs more powerfully than the rPf_IL-17A/F1. Furthermore, the rPf_IL-17A/F1, 2 and 3 proteins might activate the NF-κB and MAPK signal pathways by IL-17RA, ACT1, TRAF6, TRAF2, TRAF5 and TAK1, indicating that the three Pf_IL-17A/F proteins may play different roles in promoting inflammatory response.
A Longitudinal Analysis of Handwashing and Mask-Wearing During COVID-19

The COVID-19 pandemic has seen health preventive behaviors to prevent spread of the virus become highly politicized in the United States. A clear division exists between Democrats favoring health preventive measures and Republicans often defying such measures. Amid increasing fear of the virus, the 2020 United States presidential election became central to how the pandemic should be managed. This longitudinal study examines whether the frequency of handwashing and mask-wearing changed after the United States election. The study further explores whether political partisanship played a part in the change. Results show that handwashing and mask-wearing increased among Democrats after the election. However, Republican’s use of masks and handwashing decreased. These results are explained in terms of loyalty to outgoing President Trump among Republicans and renewed feelings of efficacy among Democrats.
Glioblastoma Proximity to the Lateral Ventricle Alters Neurogenic Cell Populations of the Subventricular Zone

Despite current strategies combining surgery, radiation, and chemotherapy, glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Tumor location plays a key role in the prognosis of patients, with GBM tumors located in close proximity to the lateral ventricles (LVs) resulting in worse survival expectancy and higher incidence of distal recurrence. Though the reason for worse prognosis in these patients remains unknown, it may be due to proximity to the subventricular zone (SVZ) neurogenic niche contained within the lateral wall of the LVs. We present a novel rodent model to analyze the bidirectional signaling between GBM tumors and cells contained within the SVZ. Patient-derived GBM cells expressing GFP and luciferase were engrafted at locations proximal, intermediate, and distal to the LVs in immunosuppressed mice. Mice were either sacrificed after 4 weeks for immunohistochemical analysis of the tumor and SVZ or maintained for survival analysis. Analysis of the GFP+ tumor bulk revealed that GBM tumors proximal to the LV show increased levels of proliferation and tumor growth than LV-distal counterparts and is accompanied by decreased median survival. Conversely, numbers of innate proliferative cells, neural stem cells (NSCs), migratory cells and progenitors contained within the SVZ are decreased as a result of GBM proximity to the LV. These results indicate that our rodent model is able to accurately recapitulate several of the clinical aspects of LV-associated GBM, including increased tumor growth and decreased median survival. Additionally, we have found the neurogenic and cell division process of the SVZ in these adult mice is negatively influenced according to the presence and proximity of the tumor mass. This model will be invaluable for further investigation into the bidirectional signaling between GBM and the neurogenic cell populations of the SVZ.
Editorial: POSEIDON’s Stratification of ‘Low Prognosis’ Patients in ART: The WHY, the WHAT, and the HOW

1 ANDROFERT, Andrology and Human Reproduction Clinic, Campinas, Brazil, 2 Faculty of Health, Aarhus University, Aarhus, Denmark, 3 Laboratory of Reproductive Biology, Faculty of Health and Medical Sciences, University Hospital of Copenhagen, Copenhagen, Denmark, 4 Fertility Center Hamburg, Hamburg, Germany, 5 Fertility Clinic Skive, Skive Regional Hospital, Skive, Denmark, 6 Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples, Federico II, Naples, Italy
Using Tactile Sensing to Improve the Sample Efficiency and Performance of Deep Deterministic Policy Gradients for Simulated In-Hand Manipulation Tasks

Deep Reinforcement Learning techniques demonstrate advances in the domain of robotics. One of the limiting factors is a large number of interaction samples usually required for training in simulated and real-world environments. In this work, we demonstrate for a set of simulated dexterous in-hand object manipulation tasks that tactile information can substantially increase sample efficiency for training (by up to more than threefold). We also observe an improvement in performance (up to 46%) after adding tactile information. To examine the role of tactile-sensor parameters in these improvements, we included experiments with varied sensor-measurement accuracy (ground truth continuous values, noisy continuous values, Boolean values), and varied spatial resolution of the tactile sensors (927 sensors, 92 sensors, and 16 pooled sensor areas in the hand). To facilitate further studies and comparisons, we make these touch-sensor extensions available as a part of the OpenAI Gym Shadow-Dexterous-Hand robotics environments.
Integrating External and Internal Load for Monitoring Fitness and Fatigue Status in Standard Microcycles in Elite Rink Hockey

The aims of this study were 3-fold: firstly, to present an integrative approach to external and internal load dynamics for monitoring fitness and fatigue status of specific in-court rink hockey training sessions in a standard microcycle; secondly, to assess the differences between training sessions and matches; the third and final aim was to assess the association between external and internal load metrics. The external load, using a local positioning system, and internal load, using the declared rate of perceived exertion, were measured during 23 in-season microcycles for nine top-level players. Training load data were analysed with regard to the number of days before or after a match [match day (MD) minus or plus]. In relation to the first aim, internal and external load metrics merged into a single integrated system using pooled data z-scores provided an invisible monitoring tool that places the players in the fitness-fatigue continuum throughout the different microcycle sessions. In this regard, MD-4 and MD-1 sessions tend to place, with a low dispersion, the players in a “low external and internal load” zone. On the contrary, in MD-3 and MD-2 sessions, as well as in MD, in which higher loads were recorded, most of the players were within a “high external and internal load” zone with a tendency towards dispersion towards the fitness or fatigue zones. Finally, and with regard to the second and third aims, an inverted “U-shape” load dynamic related to the specific goals of each training session was the main finding in terms of comparison between MD; a load peak between MD-3 and MD-2 sessions and a significant decrease in all the load variables in MD-1 sessions were found; and high-to-low correlations were found between external and internal load metrics. This study presents an integrative approach to the external and internal load of players for monitoring fitness and fatigue status during a standard microcycle in rink hockey that might provide team sport staff members with a deeper understanding of load distribution in the microcycle in relation to the match.
Naturally Occurring Bioactives as Antivirals: Emphasis on Coronavirus Infection

The current coronavirus disease (COVID-19) outbreak is a significant threat to human health and the worldwide economy. Coronaviruses cause a variety of diseases, such as pneumonia-like upper respiratory tract illnesses, gastroenteritis, encephalitis, multiple organ failure involving lungs and kidneys which might cause death. Since the pandemic started there have been more than 107 million COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ∼2.4 million deaths globally. SARS-CoV-2 is easily transmitted from person-to-person and has spread quickly across all continents. With the continued increase in morbidity and mortality caused by COVID-19, and the damage to the global economy, there is an urgent need for effective prevention and treatment strategies. The advent of safe and effective vaccines has been a significant step forward in the battle against COVID-19, however treatment of the symptoms associated with the disease still requires new anti-viral and anti-inflammatory drug therapies. To this end, scientists have been investigating available natural products that may be effective against SARS-CoV-2, with some products showing promise in fighting several viral infections. Since many natural products are dietary components or are prepared as dietary supplements people tend to consider them safer than synthetic drugs. For example, Traditional Chinese Medicines have been effectively utilized to treat SARS-CoV-2 infected patients with promising results. In this review, we summarize the current knowledge of COVID-19 therapies and the therapeutic potential of medicinal plant extracts and natural compounds for the treatment of several viral infections, with special emphasis on SARS-CoV-2 infection. Realistic strategies that can be employed for the effective use of bioactive compounds for anti-SARS-CoV-2 research are also provided.