Miracle-dz/UniFAR-FTUs huggingface dataset:
Target of rapamycin controls hyphal growth and pathogenicity through FoTIP4 in Fusarium oxysporum

Abstract Fusarium oxysporum is the causal agent of the devastating Fusarium wilt by invading and colonizing the vascular system in various plants, resulting in substantial economic losses worldwide. Target of rapamycin (TOR) is a central regulator that controls intracellular metabolism, cell growth, and stress responses in eukaryotes, but little is known about TOR signalling in F. oxysporum. In this study, we identified conserved FoTOR signalling pathway components including FoTORC1 and FoTORC2. Pharmacological assays showed that F. oxysporum is hypersensitive to rapamycin in the presence of FoFKBP12 while the deletion mutant strain ΔFofkbp12 is insensitive to rapamycin. Transcriptomic data indicated that FoTOR signalling controls multiple metabolic processes including ribosome biogenesis and cell wall‐degrading enzymes (CWDEs). Genetic analysis revealed that FoTOR1 interacting protein 4 (FoTIP4) acts as a new component of FoTOR signalling to regulate hyphal growth and pathogenicity of F. oxysporum. Importantly, transcript levels of genes associated with ribosome biogenesis and CWDEs were dramatically downregulated in the ΔFotip4 mutant strain. Electrophoretic mobility shift assays showed that FoTIP4 can bind to the promoters of ribosome biogenesis‐ and CWDE‐related genes to positively regulate the expression of these genes. These results suggest that FoTOR signalling plays central roles in regulating hyphal growth and pathogenicity of F. oxysporum and provide new insights into FoTOR1 as a target for controlling and preventing Fusarium wilt in plants.
HiChIP and Hi-C Protocol Optimized for Primary Murine T Cells

The functional implications of the three-dimensional genome organization are becoming increasingly recognized. The Hi-C and HiChIP research approaches belong among the most popular choices for probing long-range chromatin interactions. A few methodical protocols have been published so far, yet their reproducibility and efficiency may vary. Most importantly, the high frequency of the dangling ends may dramatically affect the number of usable reads mapped to valid interaction pairs. Additionally, more obstacles arise from the chromatin compactness of certain investigated cell types, such as primary T cells, which due to their small and compact nuclei, impede limitations for their use in various genomic approaches. Here we systematically optimized all the major steps of the HiChIP protocol in T cells. As a result, we reduced the number of dangling ends to nearly zero and increased the proportion of long-range interaction pairs. Moreover, using three different mouse genotypes and multiple biological replicates, we demonstrated the high reproducibility of the optimized protocol. Although our primary goal was to optimize HiChIP, we also successfully applied the optimized steps to Hi-C, given their significant protocol overlap. Overall, we describe the rationale behind every optimization step, followed by a detailed protocol for both HiChIP and Hi-C experiments.
Exploring Ripple Waves in the Human Brain

Ripples are brief (<150 ms) high-frequency oscillatory neural activities in the brain with a range of 140 to 200 Hz in rodents and 80 to 140 Hz in humans. Ripples are regarded as playing an essential role in several aspects of memory function, mainly in the hippocampus. This type of ripple generally occurs with sharp waves and is called a sharp-wave ripple (SPW-R). Extensive research of SPW-Rs in the rodent brain while actively awake has also linked the function of these SPW-Rs to navigation and decision making. Although many studies with rodents unveiled SPW-R function, research in humans on this subject is still sparse. Therefore, unveiling SPW-R function in the human hippocampus is warranted. A certain type of ripples may also be a biomarker of epilepsy. This type of ripple is called a pathological ripple (p-ripple). p-ripples have a wider range of frequency (80-500 Hz) than SPW-Rs, and the range of frequency is especially higher in brain regions that are intrinsically linked to epilepsy onset. Brain regions producing ripples are too small for scalp electrode recording, and intracranial recording is typically needed to detect ripples. In addition, SPW-Rs in the human hippocampus have been recorded from patients with epilepsy who may have p-ripples. Differentiating SPW-Rs and p-ripples is often not easy. We need to develop more sophisticated methods to record SPW-Rs to differentiate them from p-ripples. This paper reviews the general features and roles of ripple waves.
Engineering Dirhodium Artificial Metalloenzymes for Diazo Coupling Cascade Reactions.

Artificial metalloenzymes (ArMs) are commonly used to control the stereoselectivity of catalytic reactions, but controlling chemoselectivity remains challenging. In this study, we engineer a dirhodium ArM to catalyze diazo cross-coupling to form an alkene that, in a one-pot cascade reaction, is reduced to an alkane with high enantioselectivity (typically >99% e.e.) by an alkene reductase. The numerous protein and small molecule components required for the cascade reaction had minimal effect on ArM catalysis. Directed evolution of the ArM led to improved yields and E/Z selectivities for a variety of substrates, which translated to cascade reaction yields. MD simulations of ArM variants were used to understand the structural role of the cofactor on ArM conformational dynamics. These results highlight the ability of ArMs to control both catalyst stereoselectivity and chemoselectivity to enable reactions in complex media that would otherwise lead to undesired side reactions.
Agarose Micro‐Well Platform for Rapid Generation of Homogenous 3D Tumor Spheroids

In recent years, 3D culture of tumor spheroids has managed to revolutionize cancer research and drug discovery. 2D monolayer cells grown in cell culture flasks undergo radical changes in cell behavior, structure, and function owing to varying environmental cues and are unable to provide predictive data for preclinical evaluation. 3D tumor spheroids can better recapitulate tumor architecture, cell‒cell and cell‒matrix connectivity, and the tissue complexity of tumors grown in animal models. However, many of the existing techniques to culture 3D spheroids are time‐consuming and ineffective and produce irregular‐shaped spheroids that cannot be easily incorporated in biological assays. The set of protocols described herein makes use of a commercial hair brush as a template to create concave micro‐well impressions in agarose. This technique is easy, inexpensive, and adaptable and also has the ability to produce uniform, homogenous cancer spheroids, with large diameter (∼1000 μm) and thickness (∼250 μm), within 24 to 48 hr after cell seeding. The 3D spheroids produced using the agarose micro‐well platform function as an excellent 3D in vitro model for understanding the extent of penetration, uptake, and distribution of targeted cargos such as a diagnostic or therapeutic agents for identification and treatment of cancer. © 2021 Wiley Periodicals LLC.
Be My Safe Haven: Parent–Child Relationships and Emotional Health During COVID-19

Abstract Objective Since March 2020, millions of children have been confined to their homes and restricted from in-person activities, radically changing the dynamics of parent–child relationships. This study examines the association between coronavirus disease 2019 (COVID-19) impact and the mental health of parents and school-aged children; specifically, whether qualities of the parent–child relationship moderated the relationship between parents’ emotional health (EH) and children’s emotional and behavioral health (EBH). Methods Data from this Internet-based study of a community sample were collected in March–May 2020. Parents (N = 158, 92.4% White, 96.2% female) reported on COVID-19 impacts, their own EH, perceptions of their relationship with their eldest child between 6 and 12 years-old, and the EBH of that child. Results Responses to questions about COVID-19 impact were assigned weighted values and used to create a COVID-19 impact scale. Hierarchical linear regressions revealed that greater COVID-19 impact was associated with greater parents’ EH issues only, and parents’ EH was a significant positive predictor of children’s EBH. Positive qualities and conflict in the parent–child relationship moderated the link between parents’ and children’s EH. At higher levels of relationship conflict and lower levels of positivity, there were stronger positive associations between parents’ and children’s EH. Parent–child relationship quality did not moderate the association between parents’ EH and children’s behavioral health (BH). Conclusions These cross-sectional study results suggest that beyond focusing on symptom management, families may benefit from supports targeting the parent–child relationship. Insights and implications for practitioners are discussed.
Fruit and Vegetable Consumption and the Risk of Prostate Cancer: A Systematic Review and Meta-Analysis

Abstract Background Emerging researches has evaluated whether fruit and vegetable consumption reduce the risk of prostate cancer. However, the conclusions of published articles remained confusing. Thus, we conducted an updated systematic review and meta-analysis to confirm the relationship of fruit and vegetable consumption and the risk of prostate cancer. Method We searched PubMed, EMBASE, Web of Science and Chinese National Knowledge Infrastructure (CNKI) up to September 1, 2020. We finally included 17 cohort studies related to fruit or vegetable intake after rigid quality assessment and checking references of the retrieved articles and relevant reviews. Newcastle–Ottawa scale was adopted to assess the quality of studies and random effect model with RR and 95% CI were used to assess the risk. Results No significant relationship was found between fruit consumption (RR = 1.00, 95% CI = 0.94–1.05) and vegetable consumption (RR = 0.98, 95% CI = 0.94–1.02) and the risk of prostate cancer. No significant heterogeneity or publication bias was identified. Conclusion Our updated meta-analysis demonstrated that fruit and vegetable consumption can barely reduce the risk of prostate cancer with several limitations. Further clinical and basic researches are eagerly awaited to confirm our results and clarify the potential biological mechanisms.
Does the Time of Day at Which Endocrine Therapy Is Taken Affect Breast Cancer Patient Outcomes?

Background: Non-compliance and non-persistence with endocrine therapy for breast cancer is common and usually related to treatment-induced side effects. There are anecdotal reports that simply changing the time of day when taking endocrine therapy (i.e., changing morning dosing to evening dosing or vice versa) can reduce side effects. Literature review: We conducted a literature review to evaluate whether changing the timing of tamoxifen and/or aromatase inhibitor administration impacted patient outcomes. No randomized control trials or prospective cohort studies that looked at time of day of endocrine therapy were identified through our review of literature from 1947 until August 2020. Conclusions: Given the rates of endocrine therapy non-compliance and non-persistence reported in the literature, ranging from 41–72% and 31–73%, respectively, simply changing the time of day when medications are taken could be an important strategy. We could identify no trials evaluating the effect of changes in timing of administration of endocrine therapy on breast cancer patient outcomes. Randomized control trials are clearly indicated for this simple and cost-effective intervention.
Artificial hyperventilation normalizes haemodynamics and arterial oxygen content in hypoxic rats

Background Although humans are capable of enduring critically low levels of oxygen, many hypoxaemic patients die despite aggressive therapies. Mimicking the physiological hyperventilation necessary to survive extreme hypoxic conditions could minimize the derangements caused by acute hypoxic-hypoxia. The objective of this study was to measure the haemodynamic-biochemical response to artificially induced hyperventilation in hypoxic rats. Methods Twenty-four deeply anaesthetized and mechanically ventilated rats were allocated to 3 groups: control (n = 5, FiO2 = 1); hypoxic spontaneously hyperventilating (n = 10, FiO2 = 0.08); and hypoxic artificially induced hyperventilation (n = 9, targeting PaCO2 = 10 mm Hg, FiO2 = 0.08). We compared the spontaneously and artificially hyperventilating groups. P-values < 0.01 were considered statistically significant. Mean arterial pressure (MAP) and serum chemistry were measured for 180 minutes. Results The control group remained stable throughout the experiment. The hypoxic groups developed profound hypotension after the decrease in FiO2. However, the arti-ficially induced hyperventilated rats recovered their MAP to levels higher than the spontaneously hyperventilating group (117.1 ± 17.2 vs. 68.1 ± 16.0, P = 0.0048). In regard to the biochemical derangements, even though the serum lactate and PaO2 were not different among the hypoxic groups, the artificially hyperventilated group achieved significantly higher SaO2 (94.3 ± 3.6 vs. 58.6 ± 9.6, P = 0.005), pH (7.87 ± 0.04 vs. 7.50 ± 0.13, P = 0.005), and CaO2 (17.7 ± 2.6 vs. 10.2 ± 1.3, P = 0.005) at 180 minutes. Conclusions Artificially induced hyperventilation led to the correction of arterial oxygen content, severe serum chemistry, and haemodynamic derangements. These findings may represent a novel rescue manoeuvre and serve as a bridge to a permanent form of support, but should be further studied before being translated to the clinical setting.
Neutrophil extracellular traps induce a hypercoagulable state in glioma

Venous thromboembolism (VTE) is one of the leading complications in glioma patients. Neutrophil extracellular traps (NETs) have been reported to play a critical role in the physiopathology of cancer. We aimed to investigate the presence and potential role of NETs in the hypercoagulable state in glioma patients. Moreover, we evaluated the interaction between NETs and endothelial cells (ECs) in glioma patients.
Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors

Type 2 DCs (DC2s) comprise the majority of conventional DCs within most tumors; however, little is known about their ability to initiate and sustain antitumor immunity, as most studies have focused on antigen cross-presenting DC1s. Here, we report that DC2 infiltration identified by analysis of multiple human cancer data sets showed a significant correlation with survival across multiple human cancers, with the benefit being seen in tumors resistant to cytotoxic T cell control. Characterization of DC subtype infiltration into an immunotherapy-resistant model of breast cancer revealed that impairment of DC1s through 2 unique models resulted in enhanced DC2 functionality and improved tumor control. BATF3 deficiency depleted intratumoral DC1s, which led to increased DC2 lymph node migration and CD4+ T cell activation. Enhancing DC2 stimulatory potential by genetic deletion of Hsp90b1 (encoding molecular chaperon GP96) led to a similar enhancement of T cell immunity and improved survival in a spontaneous breast cancer model. These data highlight the therapeutic and prognostic potential of DC2s within checkpoint blockade–resistant tumors.
Using 360° immersive videos to assess paranoia in a non-clinical population

ABSTRACT Introduction: For the past two decades, virtual reality (VR) has proven to be an innovative approach for the assessment of state paranoia. However, the use of VR remains costly, and avatars are still far from realistic in terms of facial and bodily expressions. The present study aimed to test the validity of three 360° immersive videos (360IVs) as an accessible and realistic alternative for the assessment of non-clinical state paranoia. Method: Three 360IVs were created (a Lift, a Library and a Bar) and included actors behaving naturally. One hundred and fifty healthy students were assessed in terms of their proneness towards trait paranoia, were then exposed to one of the three 360IVs, and finally completed measures of state paranoia, sense of presence and cybersickness. Results : Results revealed the presence of various interpretations about the actor’s attitudes in the three 360IVs. Also, paranoid thoughts were predicted by proneness towards trait paranoia in two out of the three 360IVs. Furthermore, moderate levels of sense of presence and low levels of cybersickness were observed for each 360IV. Conclusion: The present study provides evidence in favour of the use of 360IVs as a new accessible, realistic, and standardised tool to assess state paranoia in non-clinical samples.
Key Amino Acids of M1-41 and M2-27 Determine Growth and Pathogenicity of Chimeric H17 Bat Influenza Virus in Cells and in Mice

The M1 and M2 proteins influence the morphology, replication, virulence, and transmissibility of influenza viruses. Although a few key residues in the M1 and M2 proteins have been identified, whether other residues of the M1 and M2 proteins are involved in viral replication and pathogenicity remains to be discovered. ABSTRACT Based on our previous studies, we show that the M gene is critical for the replication and pathogenicity of the chimeric H17 bat influenza virus (Bat09:mH1mN1) by replacing the bat M gene with those from human and swine influenza A viruses. However, the key amino acids of the M1 and/or M2 proteins that are responsible for virus replication and pathogenicity remain unknown. In this study, replacement of the PR8 M gene with the Eurasian avian-like M gene from the A/California/04/2009 pandemic H1N1 virus significantly decreased viral replication in both mammalian and avian cells in the background of the chimeric H17 bat influenza virus. Further studies revealed that M1 was more crucial for viral growth and pathogenicity than M2 and that the amino acid residues M1-41V and M2-27A were responsible for these characteristics in cells and in mice. These key residues of the M1 and M2 proteins identified in this study might be important for influenza virus surveillance and could be used to produce live attenuated vaccines in the future. IMPORTANCE The M1 and M2 proteins influence the morphology, replication, virulence, and transmissibility of influenza viruses. Although a few key residues in the M1 and M2 proteins have been identified, whether other residues of the M1 and M2 proteins are involved in viral replication and pathogenicity remains to be discovered. In the background of the chimeric H17 bat influenza virus, the Eurasian avian-like M gene from the A/California/04/2009 virus significantly decreased viral growth in mammalian and avian cells. Further study showed that M1 was implicated more than M2 in viral growth and pathogenicity in vitro and in vivo and that the key amino acid residues M1-41V and M2-27A were responsible for these characteristics in cells and in mice. These key residues of the M1 and M2 proteins could be used for influenza virus surveillance and live attenuated vaccine applications in the future. These findings provide important contributions to knowledge of the genetic basis of the virulence of influenza viruses.
Polysubstance Use in A Brazilian National Sample: Correlates of Co-Use of Alcohol and Prescription Drugs

Background: Responses to problem substance use have largely focused on illicit drugs, but reports on rising prescription drug misuse worldwide raise questions about their combined use with alcohol and potential consequences. The current study assessed prevalence of alcohol in conjunction with nonmedical opioid and benzodiazepine use across a nationally representative sample of adults in Brazil. Methods: Cross-sectional data on prevalence were estimated from the 2015 Brazilian Household Survey on Substance Use. We estimated past month nonmedical use of benzodiazepines and alcohol and past month nonmedical use of opioids and alcohol among adults who reported any past-year alcohol use. Zero-inflated Poisson models assessed independent correlates of alcohol and nonmedical opioid use, and alcohol and nonmedical benzodiazepine use. Results: Among adults who reported past year alcohol use, 0.4% (N = 257,051) reported past month alcohol and non-medical benzodiazepine use, and 0.5% (N = 337,333) reported past month alcohol and non-medical opioid use. Factors independently associated with co-use of alcohol and benzodiazepines included having depression (adjusted prevalence ratio (aPR):4.61 (95%CI 1.76–12.08)), anxiety (aPR:4.21 (95%CI 1.59–11.16)) and tobacco use (aPR: 5.48 (95%CI 2.26–13.27)). Factors associated with past-month alcohol and opioid use included having experienced physical or a threat of violence (aPR: 4.59 (95%CI 1.89–11.14)), and tobacco use (aPR:2.81(95%CI:1.29–6.12)). Conclusions: Co-use of prescription drugs with alcohol remains relatively rare among Brazilians, but findings point to a unique profile of persons at risk. Results of this study are important in light of changing dynamics and international markets of prescription drugs and the need for more research on use of these substances on a global scale.
Trajectories of alcohol misuse among the UK Armed Forces over a 12‐year period

Abstract Aim To identify the main trajectories of alcohol misuse among UK military personnel from 12 years after the start of the Iraq war (2003) and the factors associated with each trajectory. Design Longitudinal cohort study with three phases of data collection (2004–06, 2007–09 and 2014–16). Setting United Kingdom. Participants Serving and ex‐serving personnel of the UK Armed Forces (n = 7111) participating at Phase 1 and at least one follow‐up phase of the King's Centre for Military Health Research (KCMHR) cohort study. Measurements Trajectories of alcohol misuse were derived from scores using the Alcohol Use Disorders Identification Test (AUDIT‐10) over three data collection phases. Demographic and military characteristics were collected and, among the key covariates, post‐traumatic stress disorder (PTSD) was measured using the PTSD checklist (PCL‐C) and childhood interpersonal stress and violence was measured using items from the Adverse Childhood Experiences questionnaire. Findings Five trajectories of alcohol misuse were identified, including ‘no misuse’ (n = 2249, 31.6%) and ‘hazardous’ (n = 3398, 47.8%), ‘harmful’ (n = 832, 11.7%), ‘severe‐to‐hazardous’ (n = 258, 5.3%) and ‘severe’ (n = 374, 3.6%) drinking. Substantial changes were evident only among severe drinkers, where more than half reduced over the study period. The factors most strongly associated with belonging to harmful/severe drinking classes were young age, male gender and childhood adversities and antisocial behaviour. Severe drinkers at Phase 1 were more likely to report probable PTSD and shorter military careers and were less likely to serve as Officers. Persistent severe drinkers were less likely to serve in the RAF compared to the Army and were more likely to be reserves. Not misusing alcohol was also associated with reserve status and having left service. Conclusions In a cohort of approximately 7000 UK military personnel, trajectories of alcohol misuse appeared stable between 2004 and 2016. More than half of severe drinkers made substantial improvements over the period, but 68% of the cohort continued to drink hazardously or harmfully. Lack of change for the majority of the sample signals the need for strategies to address alcohol misuse and its cultural and psychosocial drivers.