Miracle-dz/UniFAR-FTUs huggingface dataset:
Protective role of the mitochondrial fusion protein OPA1 in hypertension

Hypertension is associated with excessive reactive oxygen species (ROS) production in vascular cells. Mitochondria undergo fusion and fission, a process playing a role in mitochondrial function. OPA1 is essential for mitochondrial fusion. Loss of OPA1 is associated with ROS production and cell dysfunction. We hypothesized that mitochondria fusion could reduce oxidative stress that defect in fusion would exacerbate hypertension. Using (a) Opa1 haploinsufficiency in isolated resistance arteries from Opa1+/− mice, (b) primary vascular cells from Opa1+/− mice, and (c) RNA interference experiments with siRNA against Opa1 in vascular cells, we investigated the role of mitochondria fusion in hypertension. In hypertension, Opa1 haploinsufficiency induced altered mitochondrial cristae structure both in vascular smooth muscle and endothelial cells but did not modify protein level of long and short forms of OPA1. In addition, we demonstrated an increase of mitochondrial ROS production, associated with a decrease of superoxide dismutase 1 protein expression. We also observed an increase of apoptosis in vascular cells and a decreased VSMCs proliferation. Blood pressure, vascular contractility, as well as endothelium‐dependent and ‐independent relaxation were similar in Opa1+/−, WT, L‐NAME‐treated Opa1+/− and WT mice. Nevertheless, chronic NO‐synthase inhibition with L‐NAME induced a greater hypertension in Opa1+/− than in WT mice without compensatory arterial wall hypertrophy. This was associated with a stronger reduction in endothelium‐dependent relaxation due to excessive ROS production. Our results highlight the protective role of mitochondria fusion in the vasculature during hypertension by limiting mitochondria ROS production.
Secondary traumatic stress, burnout, compassion satisfaction, and perceived organizational trauma readiness in forensic science professionals

Secondary traumatic stress, burnout, and compassion satisfaction have been described since the 1980s and extensively studied in first responders, law enforcement, legal professionals, and human service providers. There are few studies in forensic science professionals. To determine levels of secondary traumatic stress, burnout, and compassion satisfaction and relate these to demographics and job characteristics, we administered online a modified version of the Professional Quality of Life (ProQOL) questionnaire to professionals in crime laboratories and medical examiner offices. Participants also completed a modified version of the Vicarious Trauma‐Organizational Readiness Guide (VT‐ORG) to measure perceptions of their organizations’ efforts to address vicarious trauma and promote health and wellness. Results from 419 subjects indicated that field‐based forensic science professionals registered higher levels of secondary traumatic stress compared to laboratory‐based professionals, but burnout and compassion satisfaction were not significantly different between these groups. Demographic variables did not predict any of these outcome measures, but work with victims’ families and testifying significantly, albeit weakly, predicted higher secondary traumatic stress. Greater employee belief that their organizations were addressing issues of stress and trauma predicted lower levels of secondary traumatic stress and burnout and higher levels of compassion satisfaction. Write‐in responses by participants paralleled the quantitative findings. These results indicate a need to strengthen organizational efforts to address stress and trauma and promote health and wellness, particularly in professionals with direct field‐based exposure to crime scenes, contact with victims’ families, and responsibility for testifying.
Volumetric histological characterization of optic nerve degeneration using tissue clearing: literature review and practical study

ABSTRACT Tissue clearing technologies can greatly improve the depth and accuracy with which the three-dimensional structure of tissues, especially those of th*-e nervous system, can be visualized. A review of the present literature suggests that the growing diversity and sophistication of various approaches have contributed to the expansion of this method to a greater variety of tissue types, experimental conditions, and imaging modalities. In the proof-of-concept study presented in this paper, a simplified and modified version of the tissue clearing method CUBIC (clear, unobstructed brain imaging cocktails and computational analysis) was used in conjunction with fluorescent staining and immunohistochemistry to illustrate the three-dimensional structure and molecular characteristics of inflammatory and degenerative activity in the mouse optic nerve. Based on the studies summarized in this mini-review, and our impression from using the mCUBIC method, it appears that tissue clearing could be a viable approach revealing three-dimensional histological features of myelin-rich tissues under normal conditions and after injury.
Efficacy of Hypochlorite in Disinfesting Non-fungal Plant Pathogens in Agricultural and Horticultural Plant Production: A Meta-analysis.

Bleach products containing hypochlorite are commonly used as disinfestants to eliminate non-fungal plant pathogens from production surfaces, tools, plant surfaces, irrigation water, and produce dump tanks. While bleach products are useful, their effectiveness has been reported to vary under specific settings. A meta-analysis was conducted using 86 studies to assess the overall efficacy of hypochlorite against plant pathogenic bacteria, oomycetes and viruses and to identify factors that explain differences in product efficacy. Hypochlorite resulted in a significant (P < 0.0001) reduction in either disease intensity or propagule viability with a mean Hedges' g standardized mean difference (g+ ) of 3.01, indicating that overall, hypochlorite treatments are highly effective. However, heterogeneity in g was significant (P < 0.0001) among studies, wherein 69.8% of the variance observed in g was attributed to true effects. Further, an estimate of between-study variability was moderate (τ2 = 1.46). Random effects (RE) meta-regression showed limited effects of moderator variables dose, contact time, targeted material of treatment and organism type on product efficacy when all organism types were considered together. Since subgroup was significantly higher (P = 0.0070) for oomycetes (g+ = 3.30) than for bacteria ( g+ = 2.19), subsequent meta-regressions were performed by organism type. For oomycetes, five RE meta-regression models, each containing two moderators and their interaction, resulted in significant (P = 0.05) effects, where models with dose and time, dose and genus, time and genus, dose and target and time and target accounted for up to 50%, 71%, 57%, 48% and 47%, respectively, of the variance in true effect sizes (R2) associated with g+. For viruses, only the RE meta-regression model containing time and target and their interaction resulted in significant (P = 0.0435) effects accounting for 38% of the variance in true effect sizes associated with g+. None of the RE meta-regression models for bacteria were significant, although they still accounted for up to 28% of the variance in true effect sizes associated with g+. These results show that although the current recommended rates for dose and contact time for commercial bleach products are generally expected to result in effective disinfestation, the efficacy against non-fungal plant pathogens is expected to be influenced by the organism type and target being treated with hypochlorite.
Serial imaging of micro-agents and cancer cell spheroids in a microfluidic channel using multicolor fluorescence microscopy

Multicolor fluorescence microscopy is a powerful technique to fully visualize many biological phenomena by acquiring images from different spectrum channels. This study expands the scope of multicolor fluorescence microscopy by serial imaging of polystyrene micro-beads as surrogates for drug carriers, cancer spheroids formed using HeLa cells, and microfluidic channels. Three fluorophores with different spectral characteristics are utilized to perform multicolor microscopy. According to the spectrum analysis of the fluorophores, a multicolor widefield fluorescence microscope is developed. Spectral crosstalk is corrected by exciting the fluorophores in a round-robin manner and synchronous emitted light collection. To report the performance of the multicolor microscopy, a simplified 3D tumor model is created by placing beads and spheroids inside a channel filled with the cell culture medium is imaged at varying exposure times. As a representative case and a method for bio-hybrid drug carrier fabrication, a spheroid surface is coated with beads in a channel utilizing electrostatic forces under the guidance of multicolor microscopy. Our experiments show that multicolor fluorescence microscopy enables crosstalk-free and spectrally-different individual image acquisition of beads, spheroids, and channels with the minimum exposure time of 5.5 ms. The imaging technique has the potential to monitor drug carrier transportation to cancer cells in real-time.
Interrupting the Pathway From Discrimination to Black Adolescents' Psychosocial Outcomes: The Contribution of Parental Racial Worries and Racial Socialization Competency.

Racial discrimination can lead to psychosocial problems for Black adolescents, including internalization (e.g., depression) and externalization (e.g., conduct problems). Black parents (N = 186; Mage = 42.9) of adolescents (ages 10-18) were assessed to investigate how parental worries and racial socialization competency (i.e., confidence, skills, and stress) contribute to the association between parental discrimination experiences and their adolescents' psychosocial problems. Mediation analyses indicated that the total direct models with discrimination, worries, and problems had good fit, and that the addition of worry mediated the discrimination-problems association. Furthermore, racial socialization competency moderated the association between worry and problems, wherein greater competency was associated with less impact of worry on problems. Findings illuminate potential intervention targets for buffering discrimination's influence on adolescents' psychosocial functioning.
A study on sexual functioning and depression in Iranian women following cesarean hysterectomy due to placental abnormality after 3–6 months

ABSTRACT This study aims to investigate the prevalence of depression and impaired sexual function following the hysterectomy in Iran. This study was performed as a retrospective cohort study, from August 2017 to August 2018. Fifty-two patients with a cesarean hysterectomy and 52 with cesarean section were considered as the cases and controls, respectively. Depression and sexual function were assessed 3–6 months following the surgery in both cases and controls. Depression was evaluated by using Beck Depression Inventory (BDI) questionnaire-II-Persian. Sexual function was assessed using the Female Sexual Function Index (FSFI). The average BDI in cases was 15.37 ± 7.6 and in controls was 13.06 ± 6.7. Mild to moderate depression was detected 57.3 percent of whom with hysterectomy and 36.5 percent of whom with C/S, the BDI sum score did not differ significantly between cases and controls (p = .096). The FSFI in cases was 20.06 ± 6.96, and controls was 21.7 ± 9.83 without any significant difference (p = .364). The depression had not been significantly different between women who underwent hysterectomy and were not following 3–6 months after surgery. Furthermore, both groups had impaired sexual function after the surgery.
Integrated analysis on mRNA microarray and microRNA microarray to screen immune-related biomarkers and pathways in myelodysplastic syndrome

ABSTRACT Background Myelodysplastic syndrome (MDS) is a haematopoietic malignancy that is characterized by a heterogeneous clinical course and dysplastic maturation of blood lineages. Immune dysregulation has gained attention as one of the fundamental mechanisms responsible for the development of MDS. This study aimed to screen immune-related biomarkers and pathways in MDS. Methods Differentially expressed mRNAs (DE-mRNAs) and differentially expressed microRNAs (DE-miRNAs) in different subtypes of MDS were sourced from the Gene Expression Omnibus (GEO) database. DE-mRNAs were intersected with immune-related gene sets to collect immune-related mRNAs, which were put into the Search Tool for the Retrieval of Interacting Genes (STRING) to construct protein–protein interaction (PPI) networks. Target mRNAs of DE-miRNAs were predicted using the miRDB database and intersected with screened immune-related mRNAs to construct miRNA-mRNA interaction networks. Topological analysis of constructed networks was applied to screen key molecules, which were assessed in independent datasets and previous literature. Enrichment analysis was applied to screen dysregulated pathways in MDS. Results Screened key mRNAs were mainly from the Toll-like receptor (TLR) family, including TLR2, TLR4, TLR7, and from the chemokine family, including C-X-C motif chemokine ligand 10 (CXCL10) and CC chemokine ligand 4 (CCL4). Cytokine-cytokine receptor interactions were among the major pathways in the enrichment analysis results. Hsa-miR-30b, hsa-miR-30e and hsa-miR-221 were validated as key miRNAs and modulate cytokine-cytokine receptor interactions by targeting immune-related mRNAs. Conclusion Dysregulated cytokines reflect the immunization status in MDS. Immune-related miRNA-mRNA interactions not only provide a perspective to our understanding of immunologic derangement in the pathogenesis of MDS but also provide new therapeutic opportunities.
Climate change in the human environment: Indicators and impacts from the Fourth National Climate Assessment

ABSTRACT The Fourth National Climate Assessment (NCA4) is the most comprehensive report to date assessing climate change science, impacts, risks, and adaptation in the United States. The 1,500 page report covers a breadth of topics, ranging from foundational physical science to climate change response options. Here we present information on indicators and impacts of climate change in the human environment featured in NCA4 Volume II, focusing on: air quality, forest disturbance and wildfire, energy systems, and water resources. Observations, trends, and impacts of these aspects of our changing climate will be discussed, along with implications for the future. Implications: People of the United States are already being affected by our changing climate. Information on observed changes and impacts that affect human welfare and society, along with projections for the future, is highly valuable for informing decision-makers, including utility managers, emergency planners, and other stakeholders, about climate risk assessment, adaptation, and mitigation options.
Use of Ground Covers to Control Three-Cornered Alfalfa Hopper, Spissistilus festinus (Hemiptera: Membracidae), and Other Suspected Vectors of Grapevine Red Blotch Virus

Abstract Grapevine red blotch virus (GRBV) is the causal agent of grapevine red blotch disease, which affects wine grapes and leads to reduced crop yield and quality. The pathogen-plant-vector relationship of GRBV is not well understood; however, some possible vectors have been identified: Caladonus coquilletti (Van Duzee; Hemiptera: Cicadellidae), Colladonus reductus (Van Duzee; Hemiptera: Cicadellidae), Erythroneura spp. , Melanoliarus sp. (Hemiptera: Cixiidae), Osbornellus borealis DeLong. & Mohr (Hemiptera: Cicadellidae), Scaphytopius granticus (Ball; Hemiptera: Cicadellidae), Spissistilus festinus (Say). Of these species, S. festinus has been shown to transmit the virus to uninfected grapevines, making it of particular interest. Since the pathogen-plant-vector relationship of GRBV is not yet completely understood, pesticide use is not necessarily the best way to manage these possible vectors. Here we test if ground cover removal, by discing in spring, could reduce the activity of potential GRBV vectors. We show that S. festinus presence in the canopy was reduced in disc rows compared to just mowing the ground vegetation, whereas there were no differences in presence in the canopy between disc and mow rows of the other possible insect vectors. Erythroneura elegantula (Osborn; Hemiptera: Cicadellidae), a common pest of grapevines but not a candidate GRBV vector, was found to have higher densities in the canopy in disc rows compared to mow rows, an effect possibly mediated by changes in vine vigor associated with ground covers. We conclude that if S. festinus is a primary vector of GRBV, discing ground covers in early spring may be a viable way to reduce their presence in the vine canopy.
Surgical Trainee Performance and Alignment With Surgical Program Director Expectations

Objective: To examine the alignment between graduating surgical trainee operative performance and a prior survey of surgical program director expectations. Background: Surgical trainee operative training is expected to prepare residents to independently perform clinically important surgical procedures. Methods: We conducted a cross-sectional observational study of US general surgery residents’ rated operative performance for Core general surgery procedures. Residents’ expected performance on those procedures at the time of graduation was compared to the current list of Core general surgery procedures ranked by their importance for clinical practice, as assessed via a previous national survey of general surgery program directors. We also examined the frequency of individual procedures logged by residents over the course of their training. Results: Operative performance ratings for 29,885 procedures performed by 1861 surgical residents in 54 general surgery programs were analyzed. For each Core general surgery procedure, adjusted mean probability of a graduating resident being deemed practice-ready ranged from 0.59 to 0.99 (mean 0.90, standard deviation 0.08). There was weak correlation between the readiness of trainees to independently perform a procedure at the time of graduation and that procedure’s historical importance to clinical practice (p = 0.22, 95% confidence interval 0.01–0.41, P = 0.06). Residents also continue to have limited opportunities to learn many procedures that are important for clinical practice. Conclusion: The operative performance of graduating general surgery residents may not be well aligned with surgical program director expectations.
Structural Basis and Function of the N Terminus of SARS-CoV-2 Nonstructural Protein 1

Nonstructural protein 1 (Nsp1) of severe acute respiratory syndrome coronaviruses (SARS-CoVs) is an important pathogenic factor that inhibits host protein translation by means of its C terminus. However, its N-terminal function remains elusive. ABSTRACT Nonstructural protein 1 (Nsp1) of severe acute respiratory syndrome coronaviruses (SARS-CoVs) is an important pathogenic factor that inhibits host protein translation by means of its C terminus. However, its N-terminal function remains elusive. Here, we determined the crystal structure of the N terminus (amino acids [aa] 11 to 125) of SARS-CoV-2 Nsp1 at a 1.25-Å resolution. Further functional assays showed that the N terminus of SARS-CoVs Nsp1 alone loses the ability to colocalize with ribosomes and inhibit protein translation. The C terminus of Nsp1 can colocalize with ribosomes, but its protein translation inhibition ability is significantly weakened. Interestingly, fusing the C terminus of Nsp1 with enhanced green fluorescent protein (EGFP) or other proteins in place of its N terminus restored the protein translation inhibitory ability to a level equivalent to that of full-length Nsp1. Thus, our results suggest that the N terminus of Nsp1 is able to stabilize the binding of the Nsp1 C terminus to ribosomes and act as a nonspecific barrier to block the mRNA channel, thus abrogating host mRNA translation.
Blocking the interactions between human ACE2 and coronavirus spike glycoprotein by selected drugs: a computational perspective

The coronavirus disease of 2019 (COVID-19) has become a global pandemic with rapid rate of transmission and fatalities worldwide. Scientists have been investigating a host of drugs that may be rechanneled to fight this malaise. Thus, in this current computational study we carried out molecular docking experiments to assess the bridging potentials of some commercial drugs such as chloroquine, hydroxychloroquine, lopinavir, ritonavir, nafamostat, camostat, famotidine, umifenovir, nitazoxanide, ivermectin, and fluvoxamine at the interface between human ACE2 and the coronavirus spike glycoprotein complex. This is aimed at ascertaining the ability of these drugs to bridge and prevent the complexing of these two proteins. The crystal structure of human ACE2 and the coronavirus spike glycoprotein complex was retrieved from protein database, while the selected drugs were retrieved from PubChem data base. The proteins and drugs were prepared for docking using Cresset Flare software. The docking was completed via AutoDock Vina module in Python Prescription software. The best hit drugs with each receptor were selected and their molecular interactions were analyzed using BIOVIA’s Discovery Studio 2020. The best hit compounds on the human ACE2 were the lopinavir (-10.1 kcal/mol), ritonavir (-8.9 kcal/mol), and nafamostat (-8.7 kcal/mol). Ivermectin, nafamostat, and camostat with binding energy values -9.0 kcal/mol, -7.8 kcal/mol, and -7.4 kcal/mol respectively were the hit drugs on the coronavirus spike glycoprotein. Nafamostat showed a dual bridging potential against ACE2 and spike glycoprotein, and could therefore be a promising lead compound in the prevention and control of this disease.
All for one, though not one for all: team players in normal tissue radiobiology

Abstract Purpose As part of the special issue on ‘Women in Science’, this review offers a perspective on past and ongoing work in the field of normal (non-cancer) tissue radiation biology, highlighting the work of many of the leading contributors to this field of research. We discuss some of the hypotheses that have guided investigations, with a focus on some of the critical organs considered dose-limiting with respect to radiation therapy, and speculate on where the field needs to go in the future. Conclusions The scope of work that makes up normal tissue radiation biology has and continues to play a pivotal role in the radiation sciences, ensuring the most effective application of radiation in imaging and therapy, as well as contributing to radiation protection efforts. However, despite the proven historical value of preclinical findings, recent decades have seen clinical practice move ahead with altered fractionation scheduling based on empirical observations, with little to no (or even negative) supporting scientific data. Given our current appreciation of the complexity of normal tissue radiation responses and their temporal variability, with tissue- and/or organ-specific mechanisms that include intra-, inter- and extracellular messaging, as well as contributions from systemic compartments, such as the immune system, the need to maintain a positive therapeutic ratio has never been more urgent. Importantly, mitigation and treatment strategies, whether for the clinic, emergency use following accidental or deliberate releases, or reducing occupational risk, will likely require multi-targeted approaches that involve both local and systemic intervention. From our personal perspective as five ‘Women in Science’, we would like to acknowledge and applaud the role that many female scientists have played in this field. We stand on the shoulders of those who have gone before, some of whom are fellow contributors to this special issue.