Miracle-dz/UniFAR-FTUs huggingface dataset:
Helicobacter pylori CagA Induces Cortactin Y-470 Phosphorylation-Dependent Gastric Epithelial Cell Scattering via Abl, Vav2 and Rac1 Activation

Simple Summary Various microbial pathogens target the actin-binding protein cortactin to promote their own uptake, proliferation and spread, and exhibit proposed roles in human cancerogenesis. We aimed to study the molecular mechanisms of how the gastric pathogen Helicobacter pylori hijacks cortactin phosphorylation via tyrosine kinase Abl to trigger cancer-related signal transduction events. We discovered that cortactin phosphorylated at Y-470 recruits the signaling factor Vav2 to activate the small Rho GTPase Rac1, and finally, a cancer cell motility phenotype. We also demonstrate that phosphorylation of cortactin at Y-470 can be completely inhibited by the well-known Abl inhibitor imatinib. Imatinib is an established oral chemotherapy medication, employed for efficient systemic treatment of various cancers. These results reveal a comprehensive novel pathway for how precisely H. pylori manipulates host signaling in gastric disease development, and may pave the way for new opportunities of treatment of the outcome of infections with this pathogen, i.e., through using imatinib. Abstract The pathogen Helicobacter pylori is the first reported bacterial type-1 carcinogen playing a role in the development of human malignancies, including gastric adenocarcinoma. Cancer cell motility is an important process in this scenario, however, the molecular mechanisms are still not fully understood. Here, we demonstrate that H. pylori subverts the actin-binding protein cortactin through its type-IV secretion system and injected oncoprotein CagA, e.g., by inducing tyrosine phosphorylation of cortactin at Y-470, which triggers gastric epithelial cell scattering and motility. During infection of AGS cells, cortactin was discovered to undergo tyrosine dephosphorylation at residues Y-421 and Y-486, which is mediated through inactivation of Src kinase. However, H. pylori also profoundly activates tyrosine kinase Abl, which simultaneously phosphorylates cortactin at Y-470. Phosphorylated cortactin interacts with the SH2-domain of Vav2, a guanine nucleotide exchange factor for the Rho-family of GTPases. The cortactin/Vav2 complex then stimulates a previously unrecognized activation cascade including the small GTPase Rac1, to effect actin rearrangements and cell scattering. We hypothesize that injected CagA targets cortactin to locally open the gastric epithelium in order to get access to certain nutrients. This may disturb the cellular barrier functions, likely contributing to the induction of cell motility, which is important in gastric cancer development.
Relationship between Running Spatiotemporal Kinematics and Muscle Performance in Well-Trained Youth Female Athletes. A Cross-Sectional Study

The purpose of this cross-sectional study was to analyse the relationship of neuromuscular performance and spatiotemporal parameters in 18 adolescent distance athletes (age, 15.5 ± 1.1 years). Using the OptoGait system, the power, rhythm, reactive strength index, jump flying time, and jump height of the squat jump, countermovement jump, and eight maximal hoppings test (HT8max) and the contact time (CT), flying time (FT), step frequency, stride angle, and step length of running at different speeds were measured. Maturity offset was determined based on anthropometric variables. Analysis of variance (ANOVA) of repeated measurements showed a reduction in CT (p < 0.000) and an increase in step frequency, step length, and stride angle (p < 0.001), as the velocity increased. The HT8max test showed significant correlations with very large effect sizes between neuromuscular performance variables (reactive strength index, power, jump flying time, jump height, and rhythm) and both step frequency and step length. Multiple linear regression found this relationship after adjusting spatiotemporal parameters with neuromuscular performance variables. Some variables of neuromuscular performance, mainly in reactive tests, were the predictors of spatiotemporal parameters (CT, FT, stride angle, and VO). Rhythm and jump flying time in the HT8max test and power in the countermovement jump test are parameters that can predict variables associated with running biomechanics, such as VO, CT, FT, and stride angle.
Red Cell Distribution Width as a Prognostic Factor and Its Comparison with Lactate in Patients with Sepsis

Sepsis remains the leading cause of death in critically ill patients. Thus, regular measurement of lactate levels has been proposed in sepsis guidelines. Elevated red cell distribution width (RDW) is associated with mortality risk in patients with sepsis. This study aimed to investigate the association between RDW and the risk of other adverse outcomes in patients with sepsis and to compare the mortality discriminative ability between lactate and RDW levels. This is a single-centered, retrospective, case-control study that included 504 adult patients with sepsis in the emergency department between 1 January 2020 and 31 December 2020. Eligible patients were divided into normal (RDW ≤ 14.5%) and high (RDW > 14.5%) groups. The baseline characteristics and adverse outcomes were recorded and compared. Compared with the normal RDW group, the patients in the high RDW group had a significantly higher rate of ICU admission (48.8% vs. 32.4%, p = 0.03), septic shock (39.2% vs. 23.5%, p < 0.01), and 30-day in-hospital mortality (32.0% vs. 20.7%, p < 0.01). Furthermore, the RDW (area under curve (AUC) = 0.71) had superior mortality discriminative ability compared to lactate (AUC = 0.63) levels (p = 0.02). Clinicians could rely on this simple and rapid parameter for risk stratification to initiate prompt treatment for patients with sepsis.
Hepatitis B Virus DNA Integration, Chronic Infections and Hepatocellular Carcinoma

Hepatitis B Virus (HBV) is an Old World virus with a high mutation rate, which puts its origins in Africa alongside the origins of Homo sapiens, and is a member of the Hepadnaviridae family that is characterized by a unique viral replication cycle. It targets human hepatocytes and can lead to chronic HBV infection either after acute infection via horizontal transmission usually during infancy or childhood or via maternal–fetal transmission. HBV has been found in ~85% of HBV-related Hepatocellular Carcinomas (HCC), and it can integrate the whole or part of its genome into the host genomic DNA. The molecular mechanisms involved in the HBV DNA integration is not yet clear; thus, multiple models have been described with respect to either the relaxed-circular DNA (rcDNA) or the double-stranded linear DNA (dslDNA) of HBV. Various genes have been found to be affected by HBV DNA integration, including cell-proliferation-related genes, oncogenes and long non-coding RNA genes (lincRNAs). The present review summarizes the advances in the research of HBV DNA integration, focusing on the evolutionary and molecular side of the integration events along with the arising clinical aspects in the light of WHO’s commitment to eliminate HBV and viral hepatitis by 2030.
Single Cell Cryo-Soft X-ray Tomography Shows That Each Chlamydia Trachomatis Inclusion Is a Unique Community of Bacteria

Chlamydiae are strict intracellular pathogens residing within a specialised membrane-bound compartment called the inclusion. Therefore, each infected cell can, be considered as a single entity where bacteria form a community within the inclusion. It remains unclear as to how the population of bacteria within the inclusion influences individual bacterium. The life cycle of Chlamydia involves transitioning between the invasive elementary bodies (EBs) and replicative reticulate bodies (RBs). We have used cryo-soft X-ray tomography to observe individual inclusions, an approach that combines 40 nm spatial resolution and large volume imaging (up to 16 µm). Using semi-automated segmentation pipeline, we considered each inclusion as an individual bacterial niche. Within each inclusion, we identifyed and classified different forms of the bacteria and confirmed the recent finding that RBs have a variety of volumes (small, large and abnormal). We demonstrate that the proportions of these different RB forms depend on the bacterial concentration in the inclusion. We conclude that each inclusion operates as an autonomous community that influences the characteristics of individual bacteria within the inclusion.
Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy

Cardiovascular disease is the main cause of death worldwide, making it crucial to search for new therapies to mitigate major adverse cardiac events (MACEs) after a cardiac ischemic episode. Drugs in the class of the glucagon-like peptide-1 receptor agonists (GLP1Ra) have demonstrated benefits for heart function and reduced the incidence of MACE in patients with diabetes. Previously, we demonstrated that a short-acting GLP1Ra known as DMB (2-quinoxalinamine, 6,7-dichloro-N-[1,1-dimethylethyl]-3-[methylsulfonyl]-,6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline or compound 2, Sigma) also mitigates adverse postinfarction left ventricular remodeling and cardiac dysfunction in lean mice through activation of parkin-mediated mitophagy following infarction. Here, we combined proteomics with in silico analysis to characterize the range of effects of DMB in vivo throughout the course of early postinfarction remodeling. We demonstrate that the mitochondrion is a key target of DMB and mitochondrial respiration, oxidative phosphorylation and metabolic processes such as glycolysis and fatty acid beta-oxidation are the main biological processes being regulated by this compound in the heart. Moreover, the overexpression of proteins with hub properties identified by protein–protein interaction networks, such as Atp2a2, may also be important to the mechanism of action of DMB. Data are available via ProteomeXchange with identifier PXD027867.
Similar Features, Different Behaviors: A Comparative In Vitro Study of the Adipogenic Potential of Stem Cells from Human Follicle, Dental Pulp, and Periodontal Ligament

Dental tissue-derived mesenchymal stem cells (DT-MSCs) are a promising resource for tissue regeneration due to their multilineage potential. Despite accumulating data regarding the biology and differentiation potential of DT-MSCs, few studies have investigated their adipogenic capacity. In this study, we have investigated the mesenchymal features of dental pulp stem cells (DPSCs), as well as the in vitro effects of different adipogenic media on these cells, and compared them to those of periodontal ligament stem cells (PLSCs) and dental follicle stem cells (DFSCs). DFSC, PLSCs, and DPSCs exhibit similar morphology and proliferation capacity, but they differ in their self-renewal ability and expression of stemness markers (e.g OCT4 and c-MYC). Interestingly, DFSCs and PLSCs exhibited more lipid accumulation than DPSCs when induced to adipogenic differentiation. In addition, the mRNA levels of adipogenic markers (PPAR, LPL, and ADIPOQ) were significantly higher in DFSCs and PLSCs than in DPSCs, which could be related to the differences in the adipogenic commitment in those cells. These findings reveal that the adipogenic capacity differ among DT-MSCs, features that might be advantageous to increasing our understanding about the developmental origins and regulation of adipogenic commitment.
Aurora B Tension Sensing Mechanisms in the Kinetochore Ensure Accurate Chromosome Segregation

The accurate segregation of chromosomes is essential for the survival of organisms and cells. Mistakes can lead to aneuploidy, tumorigenesis and congenital birth defects. The spindle assembly checkpoint ensures that chromosomes properly align on the spindle, with sister chromatids attached to microtubules from opposite poles. Here, we review how tension is used to identify and selectively destabilize incorrect attachments, and thus serves as a trigger of the spindle assembly checkpoint to ensure fidelity in chromosome segregation. Tension is generated on properly attached chromosomes as sister chromatids are pulled in opposing directions but resisted by centromeric cohesin. We discuss the role of the Aurora B kinase in tension-sensing and explore the current models for translating mechanical force into Aurora B-mediated biochemical signals that regulate correction of chromosome attachments to the spindle.
Sustained Elevated Blood Pressure Accelerates Atherosclerosis Development in a Preclinical Model of Disease

The continuous relationship between blood pressure (BP) and cardiovascular events makes the distinction between elevated BP and hypertension based on arbitrary cut-off values for BP. Even mild BP elevations manifesting as high-normal BP have been associated with cardiovascular risk. We hypothesize that persistent elevated BP increases atherosclerotic plaque development. To evaluate this causal link, we developed a new mouse model of elevated BP based on adeno-associated virus (AAV) gene transfer. We constructed AAV vectors to support transfer of the hRenin and hAngiotensinogen genes. A single injection of AAV-Ren/Ang (1011 total viral particles) induced sustained systolic BP increase (130 ± 20 mmHg, vs. 110 ± 15 mmHg in controls; p = 0.05). In ApoE−/− mice, AAV-induced mild BP elevation caused larger atherosclerotic lesions evaluated by histology (10-fold increase vs. normotensive controls). In this preclinical model, atheroma plaques development was attenuated by BP control with a calcium channel blocker, indicating that a small increase in BP within a physiological range has a substantial impact on plaque development in a preclinical model of atherosclerosis. These data support that non-optimal BP represents a risk for atherosclerosis development. Earlier intervention in elevated BP may prevent or delay morbidity and mortality associated with atherosclerosis.
Surface Nano-Patterning for the Bottom-Up Growth of III-V Semiconductor Nanowire Ordered Arrays

Ordered arrays of vertically aligned semiconductor nanowires are regarded as promising candidates for the realization of all-dielectric metamaterials, artificial electromagnetic materials, whose properties can be engineered to enable new functions and enhanced device performances with respect to naturally existing materials. In this review we account for the recent progresses in substrate nanopatterning methods, strategies and approaches that overall constitute the preliminary step towards the bottom-up growth of arrays of vertically aligned semiconductor nanowires with a controlled location, size and morphology of each nanowire. While we focus specifically on III-V semiconductor nanowires, several concepts, mechanisms and conclusions reported in the manuscript can be invoked and are valid also for different nanowire materials.
Synthesis of Hybrid Organic-Inorganic Hydrotalcite-Like Materials Intercalated with Duplex Herbicides: The Characterization and Simultaneous Release Properties

In this study, a controlled-release formulation of duplex herbicides, namely, 2,4,5-trichlorophenoxybutyric acid (TBA) and 3,4-dichlorophenoxy-acetic acid (3,4D), was simultaneously embedded into Zn-Al-layered double hydroxides (LDHs). The resulting nanohybrid Zinc-Aluminium-3,4D-TBA (ZADTX) was composed of a well-ordered crystalline layered structure with increasing basal spacing from 8.9 Å to 20.0 Å in the Powder X-ray Diffraction (PXRD) with 3,4D and TBA anions located in the gallery of LDHs with bilayer arrangement. The release of 3,4D and TBA fit the pseudo-second-order model. This duplex nanohybrid possessed a well-controlled release property (53.4% release from TBA and 27.8% release from 3,4D), which was highly effective, requiring the use of a small quantity and, hence, environmentally safer.
Effect of the orientation of the harbor seal vibrissa based biomimetic cylinder on hydrodynamic forces and vortex induced frequency

The present study considered the geometric disturbance inspired by a harbor seal vibrissa of which undulated surface structures (HSV) are known as a detecting device to capture the water movement induced by prey fish. As an original research can extend to the flow control based on the biomimetic, this study aims at finding the effect of the angle of attack (AOA) on flow characteristics around the harbor seal vibrissa shaped cylinder, to cover the change of flow direction during the harbor seal’s movements and surrounding conditions. Therefore, we considered a wide range of AOA varying from 0 to 90 degree. We carried out large eddy simulation (LES) to investigate the flow around inclined vibrissa shaped cylinder for the Reynolds number (Re) of 500. The elliptic cylinder is considered for the purpose of the comparison. The difference of force coefficients between the HSV and the elliptic cylinder can be classified into three regimes of one large variation region, two invariant regimes according to AOA. In c.
Political relations and tourism: evidence from China

ABSTRACT This paper provides empirical evidence on how political relations affect the tourism market. We use monthly data to identify the pattern of short-lived effects of political shocks in the tourism market. A political relation shock has an immediate effect on Chinese outbound tourism, and then the effect is amplified in the next month before it vanishes in the following months. Particularly, the negative political shocks, namely political disputes, are responsible for most of the effects on outbound tourism. Moreover, we investigate the specific mechanism in China through which political relation shocks affect outbound tourism. We find that government interference by issuing travel warnings plays a crucial role in the mechanism. Further analysis on tourists’ demand shows that deterioration in political relations itself has no direct effects on tourists’ demand. However, when accompanied by the issuance of travel warnings, the negative political shocks significantly reduce tourists’ willingness to travel to the opposing countries.
Observation of a superradiant quantum phase transition in an intracavity degenerate Fermi gas

Description Fermionic superradiance Placing an atomic gas inside an optical cavity can have profound effects, for example, inducing long-range atomic interactions through the coupling with the cavity’s photons. Such experiments have been done with bosonic atoms but realizing them with fermions has proven trickier. Zhang et al. placed an ultracold gas of fermionic lithium-6 atoms in a cavity pumped by a laser beam orthogonal to the cavity axis. For sufficiently strong pumping, the researchers detected a checkerboard pattern in the atoms’ momentum space corresponding to a superradiant phase transition in the cavity. The Pauli exclusion principle, which applies to fermions but not bosons, slowed down the atomic dynamics. —JS Signatures of fermionic quantum statistics are observed in a gas of lithium-6 atoms coupled to an optical cavity. Coupling Bose-Einstein condensates to optical cavities has enabled the study of many-body states with long-range interactions. However, equivalent experiments with ultracold Fermi gases have remained largely unexplored. Here, we report an experimental realization of a superradiant quantum phase transition of a degenerate Fermi gas in a transversely pumped optical cavity. The self-ordering checkerboard density pattern of Fermi gases and superradiant transitions of the cavity field spontaneously emerge by increasing the pumping intensity above a threshold value. The effects of Fermi statistics are manifested by an inverse square root scaling of the threshold with atom number and the slow dynamics of low–atomic momentum states. Our work provides an ideal platform for studying nonequilibirium dynamics of many-body states for long-range interacting Fermi gases.
Adsorption of Recombinant Human β-Defensin 2 and Two Mutants on Mesoporous Silica Nanoparticles and Its Effect against Clavibacter michiganensis subsp. michiganensis

Solanum lycopersicum L. is affected among other pests and diseases, by the actinomycete Clavibacter michiganensis subsp. michiganensis (Cmm), causing important economic losses worldwide. Antimicrobial peptides (AMPs) are amphipathic cationic oligopeptides with which the development of pathogenic microorganisms has been inhibited. Therefore, in this study, we evaluate antimicrobial activity of mesoporous silica nanoparticles (MSN5.4) loaded with human β-defensin-2 (hβD2) and two mutants (TRX-hβD2-M and hβD2-M) against Cmm. hβD2, TRX-hβD2-M and hβD2-M presented a half-maximum inhibitory concentration (IC50) of 3.64, 1.56 and 6.17 μg/mL, respectively. MSNs had average particle sizes of 140 nm (SEM) and a tunable pore diameter of 4.8 up to 5.4 nm (BJH). AMPs were adsorbed more than 99% into MSN and a first release after 24 h was observed. The MSN loaded with the AMPs inhibited the growth of Cmm in solid and liquid media. It was also determined that MSNs protect AMPs from enzymatic degradation when the MSN/AMPs complexes were exposed to a pepsin treatment. An improved AMP performance was registered when it was adsorbed in the mesoporous matrix. The present study could expand the applications of MSNs loaded with AMPs as a biological control and provide new tools for the management of phytopathogenic microorganisms.
Plasma Based Protein Signatures Associated with Small Cell Lung Cancer

Simple Summary Small-cell lung cancer (SCLC) typically presents at an advanced stage and is associated with high mortality. When diagnosed at an early stage with localized disease, long-term survival can, however, be achieved. In this study, we report a comprehensive proteomic profiling of case plasmas collected at the time of diagnosis or preceding diagnosis of SCLC with the objective of identifying blood-based markers associated with disease pathogenesis. Our study reveals the occurrence of circulating protein features centered on signatures of oncogenic MYC and YAP1 that were elevated in plasmas of cases at and before the time-of-diagnosis of SCLC. We further report several proteins, particularly inflammatory markers, that were identified as elevated in plasma several years prior to the diagnosis of SCLC and that may indicate increased risk of disease. In summary, our study identifies several novel circulating proteins associated with SCLC development that may offer utility for early detection. Abstract Small-cell-lung cancer (SCLC) is associated with overexpression of oncogenes including Myc family genes and YAP1 and inactivation of tumor suppressor genes. We performed in-depth proteomic profiling of plasmas collected from 15 individuals with newly diagnosed early stage SCLC and from 15 individuals before the diagnosis of SCLC and compared findings with plasma proteomic profiles of 30 matched controls to determine the occurrence of signatures that reflect disease pathogenesis. A total of 272 proteins were elevated (area under the receiver operating characteristic curve (AUC) ≥ 0.60) among newly diagnosed cases compared to matched controls of which 31 proteins were also elevated (AUC ≥ 0.60) in case plasmas collected within one year prior to diagnosis. Ingenuity Pathway analyses of SCLC-associated proteins revealed enrichment of signatures of oncogenic MYC and YAP1. Intersection of proteins elevated in case plasmas with proteomic profiles of conditioned medium from 17 SCLC cell lines yielded 52 overlapping proteins characterized by YAP1-associated signatures of cytoskeletal re-arrangement and epithelial-to-mesenchymal transition. Among samples collected more than one year prior to diagnosis there was a predominance of inflammatory markers. Our integrated analyses identified novel circulating protein features in early stage SCLC associated with oncogenic drivers.