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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells. Selleckchem INDY inhibitor Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study. Here, we develop a feeder-free, long-term, three-dimensional (3D) culture technique for hAT2 cells derived from primary human lung tissue and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and proinflammatory genes in infected hAT2 cells, indicating a robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2 and the application of defined 3D hAT2 cultures as models for respiratory diseases.Raman spectroscopy and chemometric analyses are used to characterize phenotypes of biological samples. The approach is relevant in biotechnology to identify and monitor productive cell cultures. It can also detect the presence of pathogens in food products and screen for disease in clinical applications. Raman-based phenotyping is of interest because it is inexpensive, rapid, label-free, and is not obscured by water molecules. Here, recent applications in microbial species and tissue identification, isogenic cell/tissue phenotype changes, and characterizing biological fluids were surveyed along with the myriad spectral processing and chemometric analysis approaches. Suggestions are also given to help standardize and solidify Raman-based phenotyping as an -omics analysis method. These include offering repositories for raw spectral data and molecular assignment libraries.The brain is composed of many functionally distinct areas. This organization supports distributed processing, and requires the coordination of signals across areas. Our understanding of how populations of neurons in different areas interact with each other is still in its infancy. As the availability of recordings from large populations of neurons across multiple brain areas increases, so does the need for statistical methods that are well suited for dissecting and interrogating these recordings. Here we review multivariate statistical methods that have been, or could be, applied to this class of recordings. By leveraging population responses, these methods can provide a rich description of inter-areal interactions. At the same time, these methods can introduce interpretational challenges. We thus conclude by discussing how to interpret the outputs of these methods to further our understanding of inter-areal interactions.Predicting responses of marine organisms to global change requires eco-physiological assessments across the complex life cycles of species. Here, we experimentally tested the vulnerability of a demersal temperate fish (Sparus aurata) to long-lasting heatwaves, on larval, juvenile and adult life-stages. Fish were exposed to simulated coastal (18 °C), estuarine (24 °C) summer temperatures, and heatwave conditions (30 °C) and their physiological responses were assessed based on cellular stress response biomarkers (heat shock protein 70 kDa, ubiquitin, antioxidant enzymes, lipid peroxidation) and phenotypic measures (histopathology, condition and mortality). Life-stage vulnerability can be ranked as larvae > adults > juveniles, based on mortality, tissue pathology and the capacity to employ cellular stress responses, reflecting the different environmental niches of each life stage. While larvae lacked acclimation capacity, which resulted in damage to tissues and elevated mortality, juveniles coped well with elevated temperature. The rapid induction of cytoprotective proteins maintained the integrity of vital organs in juveniles, suggesting adaptive phenotypic plasticity in coastal and estuarine waters. Adults displayed lower plasticity to heatwaves as they transition to deeper habitats for maturation, showing tissue damage in brain, liver and muscle. Life cycle closure of sea breams in coastal habitats will therefore be determined by larval and adult stages.Glyoxalase-1 (GLO-1) is the key enzyme in aldehyde defence in cancer cells. We here evaluated the prognostic impact and association with clinico-pathological parameters and relapse-free as well as overall survival in tumor samples from 187 breast cancer patients. The determined GLO1-immunoreactive score (GLO1-IRS) did not correlate with parameters such as grading, size, hormone receptors or ki67. However, an association of GLO1-IRS with the advanced glycation end product Nε-(carboxymethyl)lysine (p = 0.07) and HER2 (p = 0.06), and a strong correlation with VEGF (p = 0.008) was found. In survival analysis, no significant impact of GLO-1 IRS could be deduced for all patients. However, GLO1-IRS correlated with treatment by radiotherapy (p = 0.008) and high GLO1-IRS predicted a shorter relapse free survival after radiotherapy (log-rank p = 0.067). METABRIC- and TCGA expression-data were analyzed for correlation of regulatory genes of the NF-κB-pathway (RELA, RELB, IRAK1), the oxidative-stress associated transcription factor nrf2 (NFE2L2), the receptor for AGEs (AGER, RAGE) as well as enzymes associated with aldehyde defense. Here, RELA, RELB and NFE2L2 correlated significantly with GLO1 expression, but there were conflicting results between the two data sources. In conclusion, GLO1 was highly expressed in cancer cells, correlated surprisingly weak with survival, but we could show a positive association with the AGE CML as well as VEGF. Gene expression data suggest a regulation of GLO-1 mRNA via both, inflammation (NF-kB) and oxidative stress (NFE2L2) in tumors.Tuberculosis (TB) is a heterogeneous disease manifesting in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). Unlike human TB, murine infection results in uniformly high lung bacterial burdens and poorly organized granulomas. To develop a TB model that more closely resembles human disease, we infected mice with an ultra-low dose (ULD) of between 1-3 founding bacteria, reflecting a physiologic inoculum. ULD-infected mice exhibited highly heterogeneous bacterial burdens, well-circumscribed granulomas that shared features with human granulomas, and prolonged Mtb containment with unilateral pulmonary infection in some mice. We identified blood RNA signatures in mice infected with an ULD or a conventional Mtb dose (50-100 CFU) that correlated with lung bacterial burdens and predicted Mtb infection outcomes across species, including risk of progression to active TB in humans. Overall, these findings highlight the potential of the murine TB model and show that ULD infection recapitulates key features of human TB.