Miracle-dz/UniFAR-FTUs huggingface dataset:
Zika Virus Neuropathogenesis: The Different Brain Cells, Host Factors and Mechanisms Involved

Zika virus (ZIKV), despite being discovered six decades earlier, became a major health concern only after an epidemic in French Polynesia and an increase in the number of microcephaly cases in Brazil. Substantial evidence has been found to support the link between ZIKV and neurological complications in infants. The virus targets various cells in the brain, including radial glial cells, neural progenitor cells (NPCs), astrocytes, microglial and glioblastoma stem cells. It affects the brain cells by exploiting different mechanisms, mainly through apoptosis and cell cycle dysregulation. The modulation of host immune response and the inflammatory process has also been demonstrated to play a critical role in ZIKV induced neurological complications. In addition to that, different ZIKV strains have exhibited specific neurotropism and unique molecular mechanisms. This review provides a comprehensive and up-to-date overview of ZIKV-induced neuroimmunopathogenesis by dissecting its main target cells in the brain, and the underlying cellular and molecular mechanisms. We highlighted the roles of the different ZIKV host factors and how they exploit specific host factors through various mechanisms. Overall, it covers key components for understanding the crosstalk between ZIKV and the brain.
Automated Seismo-Volcanic Event Detection Applied to Stromboli (Italy)

Many active volcanoes exhibit Strombolian activity, which is typically characterized by relatively frequent mild volcanic explosions and also by rare and much more destructive major explosions and paroxysms. Detailed analyses of past major and minor events can help to understand the eruptive behavior of volcanoes and the underlying physical and chemical processes. Catalogs of these eruptions and, specifically, seismo-volcanic events may be generated using continuous seismic recordings at stations in the proximity of volcanoes. However, in many cases, the analysis of the recordings relies heavily on the manual picking of events by human experts. Recently developed Machine Learning-based approaches require large training data sets which may not be available a priori. Here, we propose an alternative user-friendly, time-saving, automated approach labelled as: the Adaptive-Window Volcanic Event Selection Analysis Module (AWESAM). This strategy of creating seismo-volcanic event catalogs consists of three main steps: 1) identification of potential volcanic events based on squared ground-velocity amplitudes, an adaptive MaxFilter, and a prominence threshold. 2) catalog consolidation by comparing and verifying the initial detections based on recordings from two different seismic stations. 3) identification and exclusion of signals from regional tectonic earthquakes. The strength of the python package is the reliable detection of very small and frequent events as well as major explosions and paroxysms. Here, it is applied to publicly accessible continuous seismic recordings from two almost equidistant stations at Stromboli volcano in Italy. We tested AWESAM by comparison with a hand-picked catalog and found that around 95% of the seismo-volcanic events with a signal-to-noise ratio above three are detected. In a first application, we derive a new amplitude-frequency relationship from over 290.000 seismo-volcanic events at Stromboli during 2019–2020 which were detected by AWESAM. The module allows for a straightforward generalization and application to other volcanoes with frequent Strombolian activity worldwide. Furthermore, this module can be implemented for volcanoes with rarer explosions.
Prediction Challenges From Errors in Tropical Pacific Sea Surface Temperature Trends

Models in the North American Multi-Model Ensemble (NMME) predict sea surface temperature (SST) trends in the central and eastern equatorial Pacific Ocean which are more positive than those observed over the period 1982–2020. These trend errors are accompanied by linear trends in the squared error of SST forecasts whose sign is determined by the mean model bias (cold equatorial bias is linked to negative trends in squared error and vice versa). The reason for this behavior is that the overly positive trend reduces the bias of models that are too cold and increases the bias of models that are too warm. The excessive positive SST trends in the models are also linked with overly positive trends in tropical precipitation anomalies. Larger (smaller) SST trend errors are associated with lower (higher) skill in predicting precipitation anomalies over the central Pacific Ocean. Errors in the linear SST trend do not explain a large percentage of variability in precipitation anomaly errors, but do account for large errors in amplitude. The predictions toward a too warm and wet tropical Pacific, especially since 2000, are strongly correlated with an increase in El Niño false alarms. These results may be relevant for interpreting the behavior of uninitialized CMIP5/6 models, which project SST trends that resemble the NMME trend errors.
Appraisal of Cinnamaldehyde Analogs as Dual-Acting Antibiofilm and Anthelmintic Agents

Cinnamaldehyde has a broad range of biological activities, which include antibiofilm and anthelmintic activities. The ever-growing problem of drug resistance and limited treatment options have created an urgent demand for natural molecules with antibiofilm and anthelmintic properties. Hence, we hypothesized that molecules with a scaffold structurally similar to that of cinnamaldehyde might act as dual inhibitors against fungal biofilms and helminths. In this regard, eleven cinnamaldehyde analogs were tested to determine their effects on fungal Candida albicans biofilm and nematode Caenorhabditis elegans. α-Methyl and trans-4-methyl cinnamaldehydes efficiently inhibited C. albicans biofilm formation (>90% inhibition at 50 μg/mL) with minimum inhibitory concentrations (MICs) of ≥ 200 μg/mL and 4-bromo and 4-chloro cinnamaldehydes exhibited anthelmintic property at 20 μg/mL against C. elegans. α-Methyl and trans-4-methyl cinnamaldehydes inhibited hyphal growth and cell aggregation. Scanning electron microscopy was employed to determine the surface architecture of C. albicans biofilm and cuticle of C. elegans, and confocal laser scanning microscopy was used to determine biofilm characteristics. The perturbation in gene expression of C. albicans was investigated using qRT-PCR analysis and α-methyl and trans-4-methyl cinnamaldehydes exhibited down-regulation of ECE1, IFD6, RBT5, UCF1, and UME6 and up-regulation of CHT4 and YWP1. Additionally, molecular interaction of these two molecules with UCF1 and YWP1 were revealed by molecular docking simulation. Our observations collectively suggest α-methyl and trans-4-methyl cinnamaldehydes are potent biofilm inhibitors and that 4-bromo and 4-chloro cinnamaldehydes are anthelmintic agents. Efforts are required to determine the range of potential therapeutic applications of cinnamaldehyde analogs.
Autophagy Blockage Reduces the Incidence of Pancreatic Ductal Adenocarcinoma in the Context of Mutant Trp53

Macroautophagy (hereafter referred to as autophagy) is a homeostatic process that preserves cellular integrity. In mice, autophagy regulates pancreatic ductal adenocarcinoma (PDAC) development in a manner dependent on the status of the tumor suppressor gene Trp53. Studies published so far have investigated the impact of autophagy blockage in tumors arising from Trp53-hemizygous or -homozygous tissue. In contrast, in human PDACs the tumor suppressor gene TP53 is mutated rather than allelically lost, and TP53 mutants retain pathobiological functions that differ from complete allelic loss. In order to better represent the patient situation, we have investigated PDAC development in a well-characterized genetically engineered mouse model (GEMM) of PDAC with mutant Trp53 (Trp53 R172H ) and deletion of the essential autophagy gene Atg7. Autophagy blockage reduced PDAC incidence but had no impact on survival time in the subset of animals that formed a tumor. In the absence of Atg7, non-tumor-bearing mice reached a similar age as animals with malignant disease. However, the architecture of autophagy-deficient, tumor-free pancreata was effaced, normal acinar tissue was largely replaced with low-grade pancreatic intraepithelial neoplasias (PanINs) and insulin expressing islet β-cells were reduced. Our data add further complexity to the interplay between Atg7 inhibition and Trp53 status in tumorigenesis.
Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine

The tumor-associated antigen mucin 1 (MUC1) is an attractive target of antitumor vaccine, but its weak immunogenicity is a big challenge for the development of vaccine. In order to enhance immune responses against MUC1, herein, we conjugated small molecular toll-like receptor 7 agonist (TLR7a) to carrier protein BSA via MUC1 glycopeptide to form a three-component conjugate (BSA-MUC1-TLR7a). Furthermore, we combined the three-component conjugate with Alum adjuvant to explore their synergistic effects. The immunological studies indicated that Alum adjuvant and built-in TLR7a synergistically enhanced anti-MUC1 antibody responses and showed Th1-biased immune responses. Meanwhile, antibodies elicited by the vaccine candidate effectively recognized tumor cells and induced complement-dependent cytotoxicity. In addition, Alum adjuvant and built-in TLR7a synergistically enhanced MUC1 glycopeptide-specific memory CD8+ T-cell immune responses. More importantly, the vaccine with the binary adjuvant can significantly inhibit tumor growth and prolong the survival time of mice in the tumor challenge experiment. This novel vaccine construct provides an effective strategy to develop antitumor vaccines.
Numerical Investigations of Liquid Film Offtake by Transverse Gas Flow in a Downcomer Annulus Geometry

Advances in computational power have enabled the application of computational fluid dynamics (CFD) to nuclear reactor safety analyses, which require accurate predictability for two-phase flow in complex geometries. This study is aimed at validating CFD simulation of liquid film off-take in a 1/10-scale downcomer of a reactor pressure vessel under emergency core coolant (ECC) bypass conditions. Even though different flow regimes can exist simultaneously in real flow, the traditional two-phase flow models used in CFD have a disadvantage with respect to regime dependency. In this study, VOF–slip, which is a hybrid model that combines volume-of-fluid (VOF) and mixture models and is offered in STAR-CCM+ 15.04, was used to simulate the film off-take phenomenon. The key parameters in the simulation were found to be the droplet diameter and interface turbulence damping coefficient. A parametric study was performed to determine the value of the parameters that yield a reasonable liquid film thickness and ECC bypass fraction which were measured at the Seoul National University (SNU) experiment facility. For the conditions of the SNU experiment, the droplet diameter was found to be 150 μm, and the interface turbulence damping coefficient was found to be in the range of 0–30. The validation results confirmed that the VOF–slip model can describe the behavior of the liquid film and the unresolved droplet appropriately. This resulted in an improvement in predicting the ECC bypass fraction in comparison to the results using the conventional VOF model.
Motor Rhythm Dissection From the Backward Circuit in C. elegans

Motor rhythm is initiated and sustained by oscillatory neuronal activity. We recently discovered that the A-class excitatory motor neurons (MNs) (A-MNs) function as intrinsic oscillators. They drive backward locomotion by generating rhythmic postsynaptic currents (rPSCs) in body wall muscles. Molecular underpinning of the rPSCs, however, is not fully elucidated. We report here that there are three types of the rPSC patterns, namely the phasic, tonic, and long-lasting, each with distinct kinetics and channel-dependence. The Na+ leak channel is required for all rPSC patterns. The tonic rPSCs exhibit strong dependence on the high-voltage-gated Ca2+ channels. Three K+ channels, the BK-type Ca2+-activated K+ channel, Na+-activated K+ channel, and voltage-gated K+ channel (Kv4), primarily inhibit tonic and long-lasting rPSCs with varying degrees and preferences. The elaborate regulation of rPSCs by different channels, through increasing or decreasing the rPSCs frequency and/or charge, correlates with the changes in the reversal velocity for respective channel mutants. The molecular dissection of different A-MNs-rPSC components therefore reveals different mechanisms for multiplex motor rhythm.
Pharmacological Enhancement of Extinction Retention in Non-stressed Adolescent Rats but Not Those Exposed to Chronic Corticosterone

Individuals exposed to chronic adverse experiences in childhood and adolescence are at increased risk of developing neuropsychiatric illnesses such as mood and anxiety disorders. Symptoms of anxiety disorders can often be reduced through exposure therapy, which is based on the process of extinction. Although chronic stress in adolescence is known to exacerbate the impaired extinction of learned fear during this period of development, it remains unclear whether exposure to stressors in adolescence qualitatively affects the mechanisms underlying fear extinction. Brain-derived neurotrophic factor (BDNF) and its principle receptor, tropomyosin receptor kinase B (TrkB), are involved in neuroplasticity underlying fear extinction. The small-molecule TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) improves fear extinction and reduces fear relapse (reinstatement) in adult mice when administered prior to extinction training but its effects in younger ages are unknown. In this study we tested whether 7,8-DHF enhances extinction retention and leads to less renewal in both stressed and non-stressed adolescent rats. Pre-extinction injection of 7,8-DHF led to lower levels of CS-elicited freezing in both the extinction and conditioning contexts in non-stressed adolescent male rats, but not in those given 7 days of corticosterone. These findings indicate that chronic stress interferes with the effectiveness of pharmacological agonism of TrkB in enhancing fear extinction in adolescence. A greater understanding of the mechanisms underlying extinction in adolescence and the effect of chronic corticosterone exposure on those mechanisms may inform a deeper understanding of the etiology and treatment of pediatric stress-related disorders.
Antimicrobial Resistance Profiles of Non-typhoidal Salmonella From Retail Meat Products in California, 2018

Non-typhoidal Salmonella remains a leading cause of foodborne illness in the United States, with food animal products serving as a key conduit for transmission. The emergence of antimicrobial resistance (AMR) poses an additional public health concern warranting better understanding of its epidemiology. In this study, 958 retail meat samples collected from January to December 2018 in California were tested for Salmonella. From multivariable logistic regression, there was a 6.47 (90% CI 2.29–18.27), 3.81 (90% CI 1.29–11.27), and 3.12 (90% CI 1.03–9.45) higher odds of contamination in samples purchased in the fall, spring, and summer than in winter months, respectively, and a 3.70 (90% CI 1.05–13.07) higher odds in ground turkey compared to pork samples. Fourteen distinct serotypes and 17 multilocus sequence types were identified among the 43 isolates recovered, with S. Kentucky (25.58%), S. Reading (18.60%), S. Infantis (11.63%), and S. Typhimurium (9.30%) comprising the top serotypes. High prevalence of resistance was observed in retail chicken isolates for streptomycin (12/23, 52.17%) and tetracycline (12/23, 52.17%), in ground turkey isolates for ampicillin (8/15, 53.34%), and in ground beef isolates for nalidixic acid (2/3, 66.67%). Fourteen (32.56%) were susceptible to all antimicrobials tested, 11 (25.58%) were resistant to one drug, and 12 (27.91%) were resistant to two drugs. The remaining six isolates (13.95%) were multidrug-resistant (MDR, ≥3 drug classes) S. Infantis (n = 4), S. Reading (n = 1), and S. Kentucky (n = 1). Whole-genome sequencing (WGS) identified 16 AMR genes and 17 plasmid replicons, including blaCTX–M–65 encoding ceftriaxone resistance and a D87Y mutation in gyrA conferring resistance to nalidixic acid and reduced susceptibility to ciprofloxacin. The IncFIB(pN55391) replicon previously identified in connection to the worldwide dissemination of pESI-like mega plasmid carriage in an emerged S. Infantis clone was detected in four of the six MDR isolates. Genotypes from WGS showed high concordance with phenotype with overall sensitivity and specificity of 95.31% and 100%, respectively. This study provides insight into the AMR profiles of a diversity of Salmonella serotypes isolated from retail meat products in California and highlights the value of routine retail food surveillance for the detection and characterization of AMR in foodborne pathogens.
Selective Depletion of Adult GFAP-Expressing Tanycytes Leads to Hypogonadotropic Hypogonadism in Males

In adult mammals, neural stem cells are localized in three neurogenic regions, the subventricular zone of the lateral ventricle (SVZ), the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the hypothalamus. In the SVZ and the SGZ, neural stem/progenitor cells (NSPCs) express the glial fibrillary acidic protein (GFAP) and selective depletion of these NSPCs drastically decreases cell proliferation in vitro and in vivo. In the hypothalamus, GFAP is expressed by α-tanycytes, which are specialized radial glia-like cells in the wall of the third ventricle also recognized as NSPCs. To explore the role of these hypothalamic GFAP-positive tanycytes, we used transgenic mice expressing herpes simplex virus thymidine kinase (HSV-Tk) under the control of the mouse Gfap promoter and a 4-week intracerebroventricular infusion of the antiviral agent ganciclovir (GCV) which kills dividing cells expressing Tk. While GCV significantly reduced the number and growth of hypothalamus-derived neurospheres from adult transgenic mice in vitro, it causes hypogonadotropic hypogonadism in vivo. The selective death of dividing tanycytes expressing GFAP indeed results in a marked decrease in testosterone levels and testicular weight, as well as vacuolization of the seminiferous tubules and loss of spermatogenesis. Additionally, GCV-treated GFAP-Tk mice show impaired sexual behavior, but no alteration in food intake or body weight. Our results also show that the selective depletion of GFAP-expressing tanycytes leads to a sharp decrease in the number of gonadotropin-releasing hormone (GnRH)-immunoreactive neurons and a blunted LH secretion. Overall, our data show that GFAP-expressing tanycytes play a central role in the regulation of male reproductive function.
Acute Myeloid Leukemia Cells Functionally Compromise Hematopoietic Stem/Progenitor Cells Inhibiting Normal Hematopoiesis Through the Release of Extracellular Vesicles

Acute myeloid leukemia (AML) is an aggressive and heterogeneous clonal disorder of hematopoietic stem/progenitor cells (HSPCs). It is not well known how leukemia cells alter hematopoiesis promoting tumor growth and leukemic niche formation. In this study, we investigated how AML deregulates the hematopoietic process of HSPCs through the release of extracellular vesicles (EVs). First, we found that AML cells released a heterogeneous population of EVs containing microRNAs involved in AML pathogenesis. Notably, AML-EVs were able to influence the fate of HSPCs modifying their transcriptome. In fact, gene expression profile of AML-EV-treated HSPCs identified 923 down- and 630 up-regulated genes involved in hematopoiesis/differentiation, inflammatory cytokine production and cell movement. Indeed, most of the down-regulated genes are targeted by AML-EV-derived miRNAs. Furthermore, we demonstrated that AML-EVs were able to affect HSPC phenotype, modifying several biological functions, such as inhibiting cell differentiation and clonogenicity, activating inflammatory cytokine production and compromising cell movement. Indeed, a redistribution of HSPC populations was observed in AML-EV treated cells with a significant increase in the frequency of common myeloid progenitors and a reduction in granulocyte-macrophage progenitors and megakaryocyte-erythroid progenitors. This effect was accompanied by a reduction in HSPC colony formation. AML-EV treatment of HSPCs increased the levels of CCL3, IL-1B and CSF2 cytokines, involved in the inflammatory process and in cell movement, and decreased CXCR4 expression associated with a reduction of SDF-1 mediated-migration. In conclusion, this study demonstrates the existence of a powerful communication between AML cells and HSPCs, mediated by EVs, which suppresses normal hematopoiesis and potentially contributes to create a leukemic niche favorable to neoplastic development.
Treatment of Androgenetic Alopecia Using PRP to Target Dysregulated Mechanisms and Pathways

Androgenetic alopecia (“AGA”) is the most prevalent type of progressive hair loss, causing tremendous psychological and social stress in patients. However, AGA treatment remains limited in scope. The pathogenesis of androgenetic alopecia is not completely understood but is known to involve a hair follicle miniaturization process in which terminal hair is transformed into thinner, softer vellus-like hair. This process is related to the dysregulation of the Wnt/β-catenin signaling pathway, which causes premature termination of the anagen growth phase in hair follicles. Historically used for wound healing, platelet rich plasma (“PRP”) has recently been at the forefront of potential AGA treatment. PRP is an autologous preparation of plasma that contains a high number of platelets and their associated growth factors such as EGF, IGF-1, and VEGF. These factors are known to individually play important roles in regulating hair follicle growth. However, the clinical effectiveness of PRP is often difficult to characterize and summarize as there are wide variabilities in the PRP preparation and administration protocols with no consensus on which protocol provides the best results. This study follows the previous review from our group in 2018 by Cervantes et al. to analyze and discuss recent clinical trials using PRP for the treatment of AGA. In contrast to our previous publication, we include recent clinical trials that assessed PRP in combination or in direct comparison with standard of care procedures for AGA such as topical minoxidil and/or oral finasteride. Overall, this study aims to provide an in-depth analysis of PRP in the treatment of AGA based on the evaluation of 17 recent clinical trials published between 2018 and October 2021. By closely examining the methodologies of each clinical trial included in our study, we additionally aim to provide an overall consensus on how PRP can be best utilized for the treatment of AGA.