Miracle-dz/UniFAR-FTUs huggingface dataset:
A Scoping Review of West Nile Virus Seroprevalence Studies among African Equids

West Nile virus (WNV) is an emerging and re-emerging zoonotic flavivirus first identified in and endemic to Africa. The virus is transmitted between birds by biting mosquitoes, with equids and humans being incidental hosts. The majority of infected incidental hosts display no or only mild clinical signs, but a fraction develop encephalitis. The aim of this scoping review was to identify and evaluate primary research on the presence of antibodies to WNV among African equids. Three bibliographic databases and the grey literature were searched. Of 283 articles identified, only 16 satisfied all the inclusion criteria. Data were collated on study design and outcomes. The overall seroprevalence reported ranged from 17.4 to 90.3%, with 1998 (35%) of the 5746 horses, donkeys and mules having screened positive for WNV antibodies. Several articles determined that seroprevalence increased significantly with age. Due to co-circulation of other flaviviruses in Africa, in the majority of studies that screened samples by ELISA, positive results were confirmed using a more specific neutralization test. However, only eight studies tested against other flaviviruses, including Potiskum, Uganda S, Wesselsbron and yellow fever virus in one, Japanese encephalitis and Usutu virus (USUV) in one, tick-borne encephalitis and USUV in one and USUV only in three. Equids are regarded as useful sentinel animals for WNV, but variation in study design poses challenges when trying to determine risk factors for, and trends in, WNV seroprevalence.
Nutritional Interventions Targeting Gut Microbiota during Cancer Therapies

The gut microbiome is increasingly being recognized for its influence on intestinal and extra-intestinal disorders such as cancer. Today, diet is the most studied environmental modulator of gut microbiota, capable of altering or improving it in terms of richness and diversity. Recent evidence from several preclinical and clinical trials suggested that gut microbiota composition could modulate cancer therapies (toxicities, treatment responses) and vice versa. This review highlights the latest research on the bidirectional associations between gut microbiota and cancer. We also dissect the role of gut microbiota during cancer therapies in terms of toxicity and treatment response and, in turn, how cancer therapies could impact gut microbiota composition and functions. In this context, we summarize the state-of-the-art research regarding the role of various nutritional interventions—prebiotics, dietary strategies, and dietary restrictions—as cutting-edge possibilities to modulate gut microbiota during cancer therapies.
Resilience of Microbial Communities after Hydrogen Peroxide Treatment of a Eutrophic Lake to Suppress Harmful Cyanobacterial Blooms

Applying low concentrations of hydrogen peroxide (H2O2) to lakes is an emerging method to mitigate harmful cyanobacterial blooms. While cyanobacteria are very sensitive to H2O2, little is known about the impacts of these H2O2 treatments on other members of the microbial community. In this study, we investigated changes in microbial community composition during two lake treatments with low H2O2 concentrations (target: 2.5 mg L−1) and in two series of controlled lake incubations. The results show that the H2O2 treatments effectively suppressed the dominant cyanobacteria Aphanizomenon klebahnii, Dolichospermum sp. and, to a lesser extent, Planktothrix agardhii. Microbial community analysis revealed that several Proteobacteria (e.g., Alteromonadales, Pseudomonadales, Rhodobacterales) profited from the treatments, whereas some bacterial taxa declined (e.g., Verrucomicrobia). In particular, the taxa known to be resistant to oxidative stress (e.g., Rheinheimera) strongly increased in relative abundance during the first 24 h after H2O2 addition, but subsequently declined again. Alpha and beta diversity showed a temporary decline but recovered within a few days, demonstrating resilience of the microbial community. The predicted functionality of the microbial community revealed a temporary increase of anti-ROS defenses and glycoside hydrolases but otherwise remained stable throughout the treatments. We conclude that the use of low concentrations of H2O2 to suppress cyanobacterial blooms provides a short-term pulse disturbance but is not detrimental to lake microbial communities and their ecosystem functioning.
Structural Investigation of Orf Virus Bcl-2 Homolog ORFV125 Interactions with BH3-Motifs from BH3-Only Proteins Puma and Hrk

Numerous viruses have evolved sophisticated countermeasures to hijack the early programmed cell death of host cells in response to infection, including the use of proteins homologous in sequence or structure to Bcl-2. Orf virus, a member of the parapoxviridae, encodes for the Bcl-2 homolog ORFV125, a potent inhibitor of Bcl-2-mediated apoptosis in the host. ORFV125 acts by directly engaging host proapoptotic Bcl-2 proteins including Bak and Bax as well as the BH3-only proteins Hrk and Puma. Here, we determined the crystal structures of ORFV125 bound to the BH3 motif of proapoptotic proteins Puma and Hrk. The structures reveal that ORFV125 engages proapoptotic BH3 motif peptides using the canonical ligand binding groove. An Arg located in the structurally equivalent BH1 region of ORFV125 forms an ionic interaction with the conserved Asp in the BH3 motif in a manner that mimics the canonical ionic interaction seen in host Bcl-2:BH3 motif complexes. These findings provide a structural basis for Orf virus-mediated inhibition of host cell apoptosis and reveal the flexibility of virus encoded Bcl-2 proteins to mimic key interactions from endogenous host signalling pathways.
Fostering “Education”: Do Extracellular Vesicles Exploit Their Own Delivery Code?

Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV “delivery code” and on the combinations of the hypothesized EV surface membrane “sender” and “recipient” molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.
Application and Perspectives of MALDI–TOF Mass Spectrometry in Clinical Microbiology Laboratories

Early diagnosis of severe infections requires of a rapid and reliable diagnosis to initiate appropriate treatment, while avoiding unnecessary antimicrobial use and reducing associated morbidities and healthcare costs. It is a fact that conventional methods usually require more than 24–48 h to culture and profile bacterial species. Mass spectrometry (MS) is an analytical technique that has emerged as a powerful tool in clinical microbiology for identifying peptides and proteins, which makes it a promising tool for microbial identification. Matrix assisted laser desorption ionization–time of flight MS (MALDI–TOF MS) offers a cost- and time-effective alternative to conventional methods, such as bacterial culture and even 16S rRNA gene sequencing, for identifying viruses, bacteria and fungi and detecting virulence factors and mechanisms of resistance. This review provides an overview of the potential applications and perspectives of MS in clinical microbiology laboratories and proposes its use as a first-line method for microbial identification and diagnosis.
Generation of a Highly Biomimetic Organoid, Including Vasculature, Resembling the Native Immature Testis Tissue

The creation of a testis organoid (artificial testis tissue) with sufficient resemblance to the complex form and function of the innate testis remains challenging, especially using non-rodent donor cells. Here, we report the generation of an organoid culture system with striking biomimicry of the native immature testis tissue, including vasculature. Using piglet testis cells as starting material, we optimized conditions for the formation of cell spheroids, followed by long-term culture in an air–liquid interface system. Both fresh and frozen-thawed cells were fully capable of self-reassembly into stable testis organoids consisting of tubular and interstitial compartments, with all major cell types and structural details expected in normal testis tissue. Surprisingly, our organoids also developed vascular structures; a phenomenon that has not been reported in any other culture system. In addition, germ cells do not decline over time, and Leydig cells release testosterone, hence providing a robust, tunable system for diverse basic and applied applications.
β-Aminobutyric Acid Induced Resistance against Alternaria Fruit Rot in Apple Fruits

Fruit body rot and calyx rot caused by Alternaria alternata f. sp. mali is an important disease of apple worldwide. The disease has recently become severe in cv. Pink Lady apple in Israel to an extent that has never been reported elsewhere in the world. No alternative control measures of the disease except fungicides are known. Here, we show for the first time that dl-β-aminobutyric acid (BABA) induces resistance against Alternaria fruit rot (AFR) in apple fruits in the laboratory and in the orchard. AFR was inhibited in fruits treated with BABA of 1000 μg/mL. BABA did not inhibit spore germination or mycelial growth of the pathogen in vitro (up to 2000 μg/mL). It was most inhibitory when applied 4 days prior to inoculation of detached fruits. BABA inhibited AFR also curatively when applied at 24 h post inoculation. Five other isomers of aminobutyric acid failed to protect the fruits from rot formation. Three field trials in commercial apple orchards proved that BABA was as protective against AFR as the commercial standard fungicidal mixture of azoxystrobin and difenoconazole. This research suggests that BABA may serve as a resistance inducer in apple against AFR. It can be used as an adequate alternative to the currently used fungicides or integrated in disease management programs to reduce fungicide load and buildup of fungicide resistance.
Pathophysiological Effects of Overactive STIM1 on Murine Muscle Function and Structure

Store-operated Ca2+ entry (SOCE) is a ubiquitous mechanism regulating extracellular Ca2+ entry to control a multitude of Ca2+-dependent signaling pathways and cellular processes. SOCE relies on the concerted activity of the reticular Ca2+ sensor STIM1 and the plasma membrane Ca2+ channel ORAI1, and dysfunctions of these key factors result in human pathologies. STIM1 and ORAI1 gain-of-function (GoF) mutations induce excessive Ca2+ influx through SOCE over-activation, and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two overlapping disorders characterized by muscle weakness and additional multi-systemic signs affecting growth, platelets, spleen, skin, and intellectual abilities. In order to investigate the pathophysiological effect of overactive SOCE on muscle function and structure, we combined transcriptomics with morphological and functional studies on a TAM/STRMK mouse model. Muscles from Stim1R304W/+ mice displayed aberrant expression profiles of genes implicated in Ca2+ handling and excitation-contraction coupling (ECC), and in vivo investigations evidenced delayed muscle contraction and relaxation kinetics. We also identified signs of reticular stress and abnormal mitochondrial activity, and histological and respirometric analyses on muscle samples revealed enhanced myofiber degeneration associated with reduced mitochondrial respiration. Taken together, we uncovered a molecular disease signature and deciphered the pathomechanism underlying the functional and structural muscle anomalies characterizing TAM/STRMK.
Ecklonia cava Extract Exerts Anti-Inflammatory Effect in Human Gingival Fibroblasts and Chronic Periodontitis Animal Model by Suppression of Pro-Inflammatory Cytokines and Chemokines

Periodontitis is one of the most common chronic inflammatory diseases. The anti-inflammatory effect of the extract from brown algae Ecklonia cava was analyzed in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGF-1), the most abundant cells in gingival tissue. The gene expressions of cyclooxygenase-2 and interleukin-6 were decreased by 78 and 50%, respectively, at 100 μg/mL Ecklonia cava extract (ECE) treatment. The gene expressions of matrix metalloproteases (MMP-2 and MMP-8) and chemokines (macrophage inflammatory protein 1-alpha and stromal cell-derived factor 1) were also significantly down-regulated by ECE treatment (p < 0.05). The increased reactive oxygen species (ROS) production in HGF-1 cells by LPS stimulation was decreased by 30% at 100 μg/mL ECE treatment. The mitogen-activated protein kinase pathway and the nuclear factor-kappa B (NF-κB) signal activated by ROS were suppressed by ECE in a dose-dependent manner. ECE treatment (400 mg/kg, 8 weeks) significantly improved alveolar bone resorption in the ligature-induced chronic periodontitis rat model. ECE supplementation also lowered elevated mRNA expression of the receptor activator of nuclear factor-kappa B (RANKL)/osteoprotegerin (OPG) in the gingival tissue (p < 0.05). Therefore, ECE mitigated gingival tissue destruction and bone resorption associated with chronic periodontitis condition.
Consequences of SUR2[A478V] Mutation in Skeletal Muscle of Murine Model of Cantu Syndrome

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the ABCC9 and KCNJ8 genes, which encode ATP-sensitive K+ (KATP) channel subunits SUR2 and Kir6.1, respectively. Most CS patients have mutations in SUR2, the major component of skeletal muscle KATP, but the consequences of SUR2 GOF in skeletal muscle are unknown. (2) Methods: We performed in vivo and ex vivo characterization of skeletal muscle in heterozygous SUR2[A478V] (SUR2wt/AV) and homozygous SUR2[A478V] (SUR2AV/AV) CS mice. (3) Results: In SUR2wt/AV and SUR2AV/AV mice, forelimb strength and diaphragm amplitude movement were reduced; muscle echodensity was enhanced. KATP channel currents recorded in Flexor digitorum brevis fibers showed reduced MgATP-sensitivity in SUR2wt/AV, dramatically so in SUR2AV/AV mice; IC50 for MgATP inhibition of KATP currents were 1.9 ± 0.5 × 10−5 M in SUR2wt/AV and 8.6 ± 0.4 × 10−6 M in WT mice and was not measurable in SUR2AV/AV. A slight rightward shift of sensitivity to inhibition by glibenclamide was detected in SUR2AV/AV mice. Histopathological and qPCR analysis revealed atrophy of soleus and tibialis anterior muscles and up-regulation of atrogin-1 and MuRF1 mRNA in CS mice. (4) Conclusions: SUR2[A478V] “knock-in” mutation in mice impairs KATP channel modulation by MgATP, markedly so in SUR2AV/AV, with atrophy and non-inflammatory edema in different skeletal muscle phenotypes.
Identification of Neurodegenerative Diseases Based on Vertical Ground Reaction Force Classification Using Time–Frequency Spectrogram and Deep Learning Neural Network Features

A novel identification algorithm using a deep learning approach was developed in this study to classify neurodegenerative diseases (NDDs) based on the vertical ground reaction force (vGRF) signal. The irregularity of NDD vGRF signals caused by gait abnormalities can indicate different force pattern variations compared to a healthy control (HC). The main purpose of this research is to help physicians in the early detection of NDDs, efficient treatment planning, and monitoring of disease progression. The detection algorithm comprises a preprocessing process, a feature transformation process, and a classification process. In the preprocessing process, the five-minute vertical ground reaction force signal was divided into 10, 30, and 60 s successive time windows. In the feature transformation process, the time–domain vGRF signal was modified into a time–frequency spectrogram using a continuous wavelet transform (CWT). Then, feature enhancement with principal component analysis (PCA) was utilized. Finally, a convolutional neural network, as a deep learning classifier, was employed in the classification process of the proposed detection algorithm and evaluated using leave-one-out cross-validation (LOOCV) and k-fold cross-validation (k-fold CV, k = 5). The proposed detection algorithm can effectively differentiate gait patterns based on a time–frequency spectrogram of a vGRF signal between HC subjects and patients with neurodegenerative diseases.
Nutraceuticals in Viral Infections: An Overview of the Immunomodulating Properties

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.
In Vivo Production of HN Protein Increases the Protection Rates of a Minicircle DNA Vaccine against Genotype VII Newcastle Disease Virus

The Cre-recombinase mediated in vivo minicircle DNA vaccine platform (CRIM) provided a novel option to replace a traditional DNA vaccine. To further improve the immune response of our CRIM vaccine, we designed a dual promoter expression plasmid named pYL87 which could synthesize short HN protein under a prokaryotic in vivo promoter PpagC and full length HN protein of genotype VII Newcastle disease virus (NDV) under the previous eukaryotic CMV promoter at the same time. Making use of the self-lysed Salmonella strain as a delivery vesicle, chickens immunized with the pYL87 construction showed an increased serum haemagglutination inhibition antibody response, as well as an increased cell proliferation level and cellular IL-4 and IL-18 cytokines, compared with the previous CRIM vector pYL47. After the virus challenge, the pYL87 vector could provide 80% protection compared to 50% protection against genotype VII NDV in pYL47 immunized chickens, indicating a promising dual promoter strategy used in vaccine design.
Improved Activity against Acute Myeloid Leukemia with Chimeric Antigen Receptor (CAR)-NK-92 Cells Designed to Target CD123

Anti-cancer activity can be improved by engineering immune cells to express chimeric antigen receptors (CARs) that recognize tumor-associated antigens. Retroviral vector gene transfer strategies allow stable and durable transgene expression. Here, we used alpharetroviral vectors to modify NK-92 cells, a natural killer cell line, with a third-generation CAR designed to target the IL-3 receptor subunit alpha (CD123), which is strongly expressed on the surface of acute myeloid leukemia (AML) cells. Alpharetroviral vectors also contained a transgene cassette to allow constitutive expression of human IL-15 for increased NK cell persistence in vivo. The anti-AML activity of CAR-NK-92 cells was tested via in vitro cytotoxicity assays with the CD123+ AML cell line KG-1a and in vivo in a patient-derived xenotransplantation CD123+ AML model. Unmodified NK-92 cells or NK-92 cells modified with a truncated version of the CAR that lacked the signaling domain served as controls. Alpharetroviral vector-modified NK-92 cells stably expressed the transgenes and secreted IL-15. Anti-CD123-CAR-NK-92 cells exhibited enhanced anti-AML activity in vitro and in vivo as compared to control NK-92 cells. Our data (1) shows the importance of IL-15 expression for in vivo persistence of NK-92 cells, (2) supports continued investigation of anti-CD123-CAR-NK cells to target AML, and (3) points towards potential strategies to further improve CAR-NK anti-AML activity.
Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response

Background: Endothelial dysfunction is central to PAH. In this study, we simultaneously analysed circulating levels of endothelial microvesicles (EMVs) and progenitor cells (PCs) in PAH and in controls, as biomarkers of pulmonary endothelial integrity and evaluated differences among PAH subtypes and as a response to treatment. Methods: Forty-seven controls and 144 patients with PAH (52 idiopathic, 9 heritable, 31 associated with systemic sclerosis, 15 associated with other connective tissue diseases, 20 associated with HIV and 17 associated with portal hypertension) were evaluated. Forty-four patients with scleroderma and 22 with HIV infection, but without PAH, were also studied. Circulating levels of EMVs, total (CD31+CD42b−) and activated (CD31+CD42b−CD62E+), as well as circulating PCs (CD34+CD133+CD45low) were measured by flow cytometry and the EMVs/PCs ratio was computed. In treatment-naïve patients, measurements were repeated after 3 months of PAH therapy. Results: Patients with PAH showed higher numbers of EMVs and a lower percentage of PCs, compared with healthy controls. The EMV/PC ratio was increased in PAH patients, and in patients with SSc or HIV without PAH. After starting PAH therapy, individual changes in EMVs and PCs were variable, without significant differences being observed as a group. Conclusion: PAH patients present disturbed vascular homeostasis, reflected in changes in circulating EMV and PC levels, which are not restored with PAH targeted therapy. Combined measurement of circulating EMVs and PCs could be foreseen as a potential biomarker of endothelial dysfunction in PAH.
Recent Advances in Transition-Metal-Free Late-Stage C-H and N-H Arylation of Heteroarenes Using Diaryliodonium Salts

Transition-metal-free direct arylation of C-H or N-H bonds is one of the key emerging methodologies that is currently attracting tremendous attention. Diaryliodonium salts serve as a stepping stone on the way to alternative environmentally friendly and straightforward pathways for the construction of C-C and C-heteroatom bonds. In this review, we emphasize the recent synthetic advances of late-stage C(sp2)-N and C(sp2)-C(sp2) bond-forming reactions under metal-free conditions using diaryliodonium salts as arylating reagent and its applications to the synthesis of new arylated bioactive heterocyclic compounds.