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Structure-Guided Design of d -Galactal Derivatives with High Affinity and Selectivity for the Galectin-8 N-Terminal Domain

Galectin-8 is a carbohydrate-binding protein that plays a crucial role in tumor progression and metastasis, antibacterial autophagy, modulation of the immune system, and bone remodeling. The design, synthesis, and protein affinity evaluation of a set of C-3 substituted benzimidazole and quinoline d-galactal derivatives identified a d-galactal-benzimidazole hybrid as a selective ligand for the gale

Mechanistic and therapeutic studies in cardiac inflammation

Cardiovascular disease (CVD) is the leading cause of death globally. Inflammatory cardiomyopathies can be life-threatening, and the underlying mechanisms are not fully understood. This thesis aimed to investigate the underlying mechanisms driving the pathogenesis of myocarditis and septic cardiomyopathy, and to explore potential treatment strategies. In particular, we focused on the pro-inflammato

Macrophage expressed tartrate-resistant acid phosphatase 5 promotes pulmonary fibrosis progression

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder involving scarring of pulmonary tissue and a subsequent decrease in respiratory capacity, ultimately resulting in death. Tartrate resistant acid phosphatase 5 (ACP5) plays a role in IPF but the exact mechanisms are yet to be elucidated. In this study, we have utilized various perturbations of the bleomycin mouse model of IPF includ

Hounsfield Unit-Calculated Bone Mineral Density Loss Following Combat-Related Lower Extremity Amputations

BACKGROUND: After combat-related lower extremity amputations, patients rapidly lose bone mineral density (BMD). As serial dual x-ray absorptiometry (DXA) scans are rarely performed in this setting, it is difficult to determine the timeline for bone loss and recovery or the role of interventions. However, a strong correlation has been demonstrated between DXA BMD and computed tomography (CT) signal

C4b-Binding Protein and Factor H Attenuate NLRP3 Inflammasome-Mediated Signalling Response during Group A Streptococci Infection in Human Cells

Introduction: Streptococcus pyogenes (group A streptococcus; GAS) is a pathogen causing over half a million deaths annually worldwide. Human immune cells respond to GAS infection by activating the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines that control infection. We investigated the role of C4b-binding protein (C4BP) and factor H (FH) in the inflammasome response to GA

Observation of an Associative State in Aqueous Hydroxide

The dynamics of chemical reactions in solution are of paramount importance in fields ranging from biology to materials science. Because the hydrogen-bond network and proton dynamics govern the behavior of aqueous solutions, they have been the subject of numerous studies over the years. Here, we report the observation of a previously unknown associative state in the hydroxide ion that forms when a

Dissection of the tonsillar cancer immune microenvironment : Perspectives of the myeloid APC – T-cell axis

Tonsillar cancer (TC) is a subset of head and neck cancer (HNC). TC incidence is sharply rising due to an increased prevalence of human papillomavirus (HPV) infection in the western world. Currently HPV status is considered during clinical staging due to its positive association to patient prognosis. Presumably, the relation between HPV and patient survival is dependent on the generation of an eff

The Gaia-ESO Survey : Oxygen Abundance in the Galactic Thin and Thick Disks

We analyze the oxygen abundances of a stellar sample representative of the two major Galactic populations: the thin and thick disks. The aim is to investigate the differences between members of the Galactic disks and contribute to the understanding of the origin of oxygen chemical enrichment in the Galaxy. The analysis is based on the [O i] = 6300.30 Å oxygen line in high-resolution spectra (R ∼ 5

Ciliated (FOXJ1+) Cells Display Reduced Ferritin Light Chain in the Airways of Idiopathic Pulmonary Fibrosis Patients

Cell-based therapies hold great promise in re-establishing organ function for many diseases, including untreatable lung diseases such as idiopathic pulmonary fibrosis (IPF). However, many hurdles still remain, in part due to our lack of knowledge about the disease-driving mechanisms that may affect the cellular niche and thereby possibly hinder the function of any transplanted cells by imposing th

3D cultivation of non-small-cell lung cancer cell lines using four different methods

PURPOSE: The aim of this study was to set up reliable and reproducible culture conditions for 3D tumoroids derived from non-small cell lung cancer (NSCLC) cell lines to enable greater opportunity for successful cultivation of patient-derived samples.METHODS: Four NSCLC cell lines, two adenocarcinomas (A549, NCI-H1975) and two squamous cell carcinomas (HCC-95, HCC-1588), were first cultured in trad

Declining Antibody Affinity Over Time After Human Vaccination With a Plasmodium falciparum Merozoite Vaccine Candidate

UNLABELLED: Maintaining high-affinity antibodies after vaccination may be important for long-lasting immunity to malaria, but data on induction and kinetics of affinity is lacking. In a phase 1 malaria vaccine trial, antibody affinity increased following a second vaccination but declined substantially over 12 months, suggesting poor maintenance of high-affinity antibodies.CLINICAL TRIALS REGISTRAT

Inflammation-profiling reveals activated pathways and biomarkers with predictive potential in oligoarticular juvenile idiopathic arthritis

Background: We set out to profile the immune mechanisms active in treatment-naïve oligoarticular JIA (oJIA) to improve the knowledge of its immunopathogenesis, to identify potential biomarkers that can aid diagnosis, predictions and that correlate with clinical disease parameters. Methods: Using Olink proteomics (inflammation panel measuring 92 markers), we defined and compared the inflammation pr

Human papillomavirus-related squamous cell carcinomas after blood or marrow transplantation - a Blood or Marrow Transplant Survivor Study report

Background Human papillomavirus (HPV) is associated with an increased risk for a variety of squamous cell carcinomas in the general population. The risk for subsequent squamous cell carcinomas in blood or marrow transplantation survivors that are potentially related to HPV (cervical, oropharyngeal, vulvar, vaginal, anal, and penile cancer; HPV-related squamous cell carcinomas) remains unknown. Met

TESS and CHEOPS discover two warm sub-Neptunes transiting the bright K-dwarf HD 15906

We report the discovery of two warm sub-Neptunes transiting the bright (G = 9.5 mag) K-dwarf HD 15906 (TOI 461, TIC 4646810). This star was observed by the Transiting Exoplanet Survey Satellite (TESS) in sectors 4 and 31, revealing two small transiting planets. The inner planet, HD 15906 b, was detected with an unambiguous period but the outer planet, HD 15906 c, showed only two transits separated

Non-typeable Haemophilus influenzae major outer membrane protein P5 contributes to bacterial membrane stability, and affects the membrane protein composition crucial for interactions with the human host

Non-typeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes a wide range of airway diseases. NTHi has a plethora of mechanisms to colonize while evading the host immune system for the establishment of infection. We previously showed that the outer membrane protein P5 contributes to bacterial serum resistance by the recruitment of complement regulators. Here, we report

The effect of climate change on avian offspring production: A global meta-analysis

Climate change affects timing of reproduction in many bird species, but few studies have investigated its influence on annual reproductive output. Here, we assess changes in the annual production of young by female breeders in 201 populations of 104 bird species (N = 745,962 clutches) covering all continents between 1970 and 2019. Overall, average offspring production has declined in recent decade

Illumination matters. Revisiting the Roman house in a new light

Interpreting the social complexity of the Roman house requires a careful evaluation of existing evidence. With this in mind, recent work in the field has proposed a variety of different approaches, focusing each time on a specific type of source (architecture and décor, ancient texts, material evidence from excavated houses), each in turn recursively deemed more adequate for the purpose or more fr

Plasma neurofilament light is a predictor of neurological outcome 12 h after cardiac arrest

Background: Previous studies have reported high prognostic accuracy of circulating neurofilament light (NfL) at 24–72 h after out-of-hospital cardiac arrest (OHCA), but performance at earlier time points and after in-hospital cardiac arrest (IHCA) is less investigated. We aimed to assess plasma NfL during the first 48 h after OHCA and IHCA to predict long-term outcomes. Methods: Observational mult