Search

The ab initio theoretical treatment of one-photon double photoionization processes has been limited to atoms and diatomic molecules by the challenges posed by large grid-based representations of the double ionized continuum wave function. To provide a path for extensions to polyatomics, an energy-adapted orbital basis approach is demonstrated that reduces the dimensions of such representations and simultaneously allows larger time steps in time-dependent computational descriptions of double ionization. Additionally, an algorithm that exploits the diagonal nature of the two-electron integrals in the grid basis and dramatically accelerates the transformation between grid and orbital representations is presented. Excellent agreement between the present results and benchmark theoretical calculations is found for H- and Be atoms, as well as the hydrogen molecule, including for the triply differential cross sections that relate the angular distribution and energy sharing of all of the particles in the molecular frame.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.

Se analizó la producción científica sobre patrimonio industrial y turismo indexada en la base de datos Scopus y se identificaron buenas prácticas, brechas, y futuras líneas de investigación, a partir de un estudio bibliométrico. Se utilizó el método bibliométrico para la búsqueda de los descriptores temáticos "heritage tourism”” and “tourism” en la base de datos Scopus, en el periodo 2013-2023. Los resultados fueron procesados mediante el software VOSviwer y Biblioshiny del paquete Bibliometrix de RstudioCloud. El estudio arrojó que en el periodo seleccionado fueron publicados en Scopus un total de 212 artículos, se destaca el año 2023 con 32 publicaciones. La revista de mayor productividad fue Sustainability con 23 artículos.

The hypoxic ventilatory response (HVR) is the increase in breathing in response to reduced arterial oxygen pressure. Over several decades, studies have revealed substantial population-level differences in the magnitude of the HVR as well as significant inter-individual variation. In particular, low HVRs occur frequently in Andean high-altitude native populations. However, our group conducted hundreds of HVR measures over several years and commonly observed low responses in sea-level populations as well. As a result, we aimed to determine the normal HVR distribution, whether low responses were common, and to what extent variation in study protocols influence these findings. We conducted a comprehensive search of the literature and examined the distributions of HVR values across 78 studies that utilized step-down/steady-state or progressive hypoxia methods in untreated, healthy human subjects. Several studies included multiple datasets across different populations or experimental conditions. In the final analysis, 72 datasets reported mean HVR values and 60 datasets provided raw HVR datasets. Of the 60 datasets reporting raw HVR values, 35 (58.3%) were at least moderately positively skewed (skew > 0.5), and 21 (35%) were significantly positively skewed (skew > 1), indicating that lower HVR values are common. The skewness of HVR distributions does not appear to be an artifact of methodology or the unit with which the HVR is reported. Further analysis demonstrated that the use of step-down hypoxia versus progressive hypoxia methods did not have a significant impact on average HVR values, but that isocapnic protocols produced higher HVRs than poikilocapnic protocols. This work provides a reference for expected HVR values and illustrates substantial inter-individual variation in this key reflex. Finally, the prevalence of low HVRs in the general population provides insight into our understanding of blunted HVRs in high-altitude adapted groups. KEY POINTS: The hypoxic ventilatory response (HVR) plays a crucial role in determining an individual's predisposition to hypoxia-related pathologies. There is notable variability in HVR sensitivity across individuals as well as significant population-level differences. We report that the normal distribution of the HVR is positively skewed, with a significant prevalence of low HVR values amongst the general healthy population. We also find no significant impact of the experimental protocol used to induce hypoxia, although HVR is greater with isocapnic versus poikilocapnic methods. These results provide insight into the normal distribution of the HVR, which could be useful in clinical decisions of diseases related to hypoxaemia. Additionally, the low HVR values found within the general population provide insight into the genetic adaptations found in populations residing in high altitudes.

Interferons (IFNs) are important signaling molecules in the human immune response against micro-organisms. Throughout initial Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) infection in vitro, inadequate IFN-γ production results in the absence of a strong T-helper 1 cell response, potentially hampering the development of an effective antibody responses in Lyme borreliosis (LB) patients. The aim of this study is to help understand the immunomodulatory mechanisms why IFN-γ production is absent in the early onset of LB. Therefore, cytokine production and STAT activation signature, following exposure of human immune cells to B. burgdorferi s.l., was investigated in vivo and in vitro. While STAT3 phosphorylation was highly induced in T cells, B cells and NK-(T) cells, STAT1 expression and IL-12p70 production were not or only slightly increased upon B. burgdorferi s.l. exposure. In response to B. burgdorferi s.l., STAT2 phosphorylation and IFNα production remained stable. STAT2 activation only increased in NK-(T) cells. In contrast, STAT4 signaling was reduced in all B. burgdorferi s.l. exposed immune cells. Moreover, B. burgdorferi s.l. significantly increased suppressor of cytokine signaling (SOCS)1 and SOCS3 gene expression in LB patients. Absence of IFN-γ production and STAT4 activation, in combination with STAT3 phosphorylation and upregulated SOCS1 and SOCS3 gene expression, suggests the formation of a more tolerant and anti-inflammatory response to B. burgdorferi s.l., specifically in T- and B-cells. In primary human PBMCs and monocyte populations, B. burgdorferi s.l. also specifically interfered with CIITA isoforms normally expressed in antigen presenting dendritic cells. In contrast, it enhanced CIITA isoforms typically present in adaptive immune cell subsets. Restoring antigen presentation capacity of innate immune cells and early production of IFN-γ in LB patients may help re-establish immune functions during initial LB. These new insights will help to understand the immunomodulatory mechanisms of B. burgdorferi s.l. during the onset of LB.

Introduction: The loss of vasculature in Spinal Cord Injury (SCI) contributes to secondary injury, expanding the injury to unharmed spinal cord (SC) regions. Understanding these mechanisms is crucial for developing therapeutic interventions. Research question: Comprehensive analysis of the temporospatial dynamics of vascular injury and regeneration following SCI. Materials and methods: Adult C57BL/6J mice were subjected to clip-compression SCI (Th 6/7, 5g, 60s, n = 20) or sham injury (laminectomy, n = 4), and sacrificed at 1, 3, 7, 14, and 28 days (d) post-injury following intracardial fluorescein isothiocyanate (FITC)-Lectin perfusion. Histological analysis (CD31, FITC-Lectin, Ki-67, IgG, TER-119) assessed vascular changes, permeability, and proliferation within the injury epicenter (region 0 (R0), ± 0,5 mm) and two adjacent SC regions (R1: ± 1 mm, R2: ± 2.5 mm). Results: Perfusion loss (FITC-Lectin+/CD31+), was most severe in R0 and R1 at d3 (p

Helicobacter pylori infection is the predominant risk factor for the development of gastric cancer. Risk is enhanced by specific H. pylori virulence factors, diet, and the inflammatory response. Chronic activation of T helper (Th) 1 and Th17 pathways contributes to prolonged inflammation; yet, higher expression of IL-17 receptor (IL-17RA) is a favorable prognostic marker for survival after gastric cancer diagnosis. The protective impact of IL-17RA signaling is not understood. To investigate if IL-17RA signaling protects during H. pylori-induced carcinogenesis, the transgenic InsGAStg/tg mouse, which is prone to H. pylori-induced gastric cancer, was utilized. InsGAStg/tg mice and InsGAStg/tgIl17ra-/- mice were infected with a cag type 4 secretion system (T4SS) positive H. pylori strain for up to 6 months. Six weeks post-infection, IL-17RA deficiency led to increased bacterial burden, increased gastritis, and development of lymphoid follicles. Increased inflammation was associated with heightened cellular proliferation and earlier loss of parietal and chief cells in InsGAStg/tgIl17ra-/- mice. Gastric cancers developed more frequently by 3- and 6-months post-infection in H. pylori-infected InsGAStg/tgIl17ra-/- mice compared to InsGAStg/tg mice. Chronic inflammation was exacerbated with IL-17RA deficiency, characterized by elevated Th1/Th17 cytokines, increased B cell infiltration, and enhanced IgA production, despite reduced expression of the polymeric immunoglobulin receptor. Further, paragastric lymph nodes of InsGAStg/tgIl17ra-/- mice were enlarged relative to controls and displayed altered gene expression profiles. Increased inflammation was accompanied by a significant increase in Cybb expression, which encodes NADPH oxidase 2, suggesting that increased oxidative damage may occur in the absence of IL-17RA. Further, there is increased phosphorylation of histone 2AX in IL-17RA deficient mice, indicating that the DNA damage response is highly activated. These data suggest that IL-17RA signaling activates a protective pathway to prevent excessive inflammation which otherwise can lead to increased oxidative stress, DNA damage, and drive gastric carcinogenesis after H. pylori infection.

Abstract: Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility– and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross– validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.