Proteomic identification of a sporozoite-specific antigen using HDAC3 inhibitor-treated tachyzoites as surrogate.

The apicomplexan parasite has a complex life cycle. Access to sexual stages and sporozoite-containing oocysts, essential for studying the parasite's environmental transmission, is limited and requires animal experiments with cats. Thus, alternatives and resource-efficient methods are needed.

Differential substrate specificity of ERK, JNK, and p38 MAP kinases toward Connexin 43.

Phosphorylation of connexin 43 (Cx43) is an important regulatory mechanism of gap junction (GJ) function. Cx43 is modified by several kinases on over 15 sites within its ∼140 amino acid-long C-terminus (CT). Phosphorylation of Cx43CT on S255, S262, S279, and S282 by ERK has been widely documented in several cell lines, by many investigators.

Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates.

mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following i.

Voices of Nanomedicine: Blueprint Guidelines for Collaboration in Addressing Global Unmet Medical Needs.

The "" under this Perspective underline the importance of interdisciplinary collaboration and partnerships across several disciplines, such as medical science and technology, medicine, bioengineering, and computational approaches, in bridging the gap between research, manufacturing, and clinical applications. Effective communication is key to bridging team gaps, enhancing trust, and resolving conflicts, thereby fostering teamwork and individual growth toward shared goals. Drawing from the success of the COVID-19 vaccine development, we advocate the application of similar collaborative models in other complex health areas such as nanomedicine and biomedical engineering.

Nationwide population-based infection- and vaccine-induced SARS-CoV-2 antibody seroprevalence in Germany in autumn/winter 2021/2022.

BackgroundThe first Corona Monitoring Nationwide (RKI-SOEP) study (October 2020-February 2021) found a low pre-vaccine SARS-CoV-2 antibody seroprevalence (2.1%) in the German adult population (≥ 18 years).AimThe objective of this second RKI-SOEP (RKI-SOEP-2) study in November 2021-March 2022 was to estimate the prevalence of SARS-CoV-2-specific anti-spike and/or anti-nucleocapsid (anti-N) IgG antibodies (combined seroprevalence), past infection based on infection-induced seroprevalence (anti-N), and basic immunisation (at least two antigen contacts through vaccination or infection) in individuals aged ≥ 14 years.

Insights into Within-Host Evolution and Dynamics of Oral and Intestinal Streptococci Unveil Niche Adaptation.

The oral-gut axis is a complex system linking the oral cavity and gastrointestinal tract, impacting host health and microbial composition. This study investigates genetic changes and adaptive mechanisms employed by streptococci-one of the few genera capable of colonizing oral and intestinal niches-within the same individual. We conducted whole-genome sequencing (WGS) on 218 streptococcal isolates from saliva and fecal samples of 14 inflammatory bowel disease (IBD) patients and 12 healthy controls.

Phenotypic and Genomic Characterization of ESBL- and AmpC-β-Lactamase-Producing Isolates from Imported Healthy Reptiles.

Background/objectives: Reptiles are known reservoirs for members of the . We investigated antimicrobial resistance (AMR) patterns, the diversity of extended-spectrum-/AmpC-β-lactamases (ESBL/AmpC) genes and the genomic organization of the ESBL/AmpC producers.

Methods: A total of 92 shipments with 184 feces, skin, and urinate samples of live healthy reptiles were obtained during border inspections at Europe's most important airport for animal trade and screened for AMR bacteria by culture, antimicrobial susceptibility testing, and whole genome sequencing (WGS) of selected isolates.

Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer.

Purpose: We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes.

Experimental Design: We conducted a two-center prospective study of patients with newly diagnosed EOC (N = 188).

BRAF and ErbB inhibitors directly activate GCN2 in an off-target manner to limit cancer cell proliferation.

Targeted kinase inhibitors are well known for their promiscuity and off-target effects. Herein, we define an off-target effect in which several clinical BRAF inhibitors, including the widely used dabrafenib and encorafenib, interact directly with GCN2 to activate the Integrated Stress Response and ATF4. Blocking this off-target effect by co-drugging with a GCN2 inhibitor in A375 melanoma cells causes enhancement rather than suppression of cancer cell outgrowth, suggesting that the off-target activation of GCN2 is detrimental to these cells.

The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing.

Protein arginine methyltransferase 5 (PRMT5) is a promising cancer target, yet it's unclear which PRMT5 roles underlie this vulnerability. Here, we establish that PRMT5 inhibition induces a special class of unspliced introns, called detained introns (DIs). To interrogate the impact of DIs, we depleted CLNS1A, a PRMT5 cofactor that specifically enables Sm protein methylation.

Designing for medication adherence in inflammatory bowel disease: multi-disciplinary approaches for self-administrable biotherapeutics.

Biotherapeutics are among the therapeutics that have revolutionized standard inflammatory bowel disease (IBD) treatment, which was previously limited to mesalamine, 5-aminosalicylic acid, corticosteroids, and classical immunosuppressants. Self-administrable biotherapeutics for IBD would enable home-based treatment and reduce the burden on medical infrastructure. Self-administration is made possible through subcutaneous injectable, oral, and rectal dosage forms.

Isolated loss of vaccine immunity in the protein losings syndrome in a patient with a reverse one and a half ventricle palliation ("failing Fontan-like physiology").

Background: A subgroup of CHDs can only be treated palliatively through a Fontan circulation. In case of a failing Fontan situation, serum proteins are lost unspecifically and can also lead to a loss of vaccine antibodies. In a failing Fontan situation, heart transplantation may be the only feasible option.

Association of mental health in childhood, adolescence and young adulthood with cardiovascular risk factors and carotid remodeling below age 30 - results from the KiGGS cohort study.

An association of mental health and in particular depression with cardiovascular disease has been shown in adults and to a lesser extent in the young. Recently improved measurement methods of carotid-intima media thickness (CIMT) and carotid stiffness (CS) allow more differentiated analyses of this link. We examined 4,361 participants of the nationwide KiGGS cohort aged 3-17 years at baseline and 14-28 years at follow-up.

Cancer immune evasion, immunoediting and intratumour heterogeneity.

Cancers can avoid immune-mediated elimination by acquiring traits that disrupt antitumour immunity. These mechanisms of immune evasion are selected and reinforced during tumour evolution under immune pressure. Some immunogenic subclones are effectively eliminated by antitumour T cell responses (a process known as immunoediting), which results in a clonally selected tumour.

High-dose intravenous BCG vaccination induces enhanced immune signaling in the airways.

Intradermal Bacillus Calmette-Guérin (BCG) is the most widely administered vaccine, but it does not sufficiently protect adults against pulmonary tuberculosis. Recent studies in nonhuman primates show that intravenous BCG administration offers superior protection against (). We used single-cell analysis of bronchoalveolar lavage cells from rhesus macaques vaccinated via different routes and doses of BCG to identify alterations in the immune ecosystem in the airway following vaccination.

Diabetes mellitus, cardiovascular and chronic respiratory diseases in Germany and Europe - results of the European Health Interview Survey (EHIS 3, 2018 - 2020).

Background: In Europe, the health situation is primarily influenced by non-communicable diseases. Comparable information on key indicators for the European region can highlight potential areas for improvement in prevention and care.

Method: Based on EHIS 3, age-standardised prevalences of three disease groups and two indicators of self-assessed health among those affected were presented for Germany ( = 22,708) and the average of 29 European countries ( = 301,960).

Utilisation of medical services in Germany and Europe - Results of the European Health Interview Survey (EHIS 3, 2018 - 2020).

Background: Needs-based care is a central concern of healthcare policy. A European comparison of the utilisation of medical services can help to assess national data and identify the need for action.

Methods: This article describes indicators on the utilisation of outpatient and inpatient services, medical examinations and the use of medicines from the third wave of the European Health Interview Survey (EHIS 3) and compares the results from Germany with the European averages.

Immunogenicity and safety of the 15-valent pneumococcal conjugate vaccine, a systematic review and meta-analysis.

Pneumococcal infections are a serious health issue associated with increased morbidity and mortality. This systematic review evaluated the efficacy, effectiveness, immunogenicity, and safety of the pneumococcal conjugate vaccine (PCV)15 compared to other pneumococcal vaccines or no vaccination in children and adults. We identified 20 randomized controlled trials (RCTs).

Wastewater-based epidemiology: deriving a SARS-CoV-2 data validation method to assess data quality and to improve trend recognition.

Introduction: Accurate and consistent data play a critical role in enabling health officials to make informed decisions regarding emerging trends in SARS-CoV-2 infections. Alongside traditional indicators such as the 7-day-incidence rate, wastewater-based epidemiology can provide valuable insights into SARS-CoV-2 concentration changes. However, the wastewater compositions and wastewater systems are rather complex.

Aging-induced changes in lymphatic muscle cell transcriptomes are associated with reduced pumping of peripheral collecting lymphatic vessels in mice.

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the gene transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing.

The T cell receptor sequence influences the likelihood of T cell memory formation.

The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual's immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells.

Modulating cell-free DNA biology as the next frontier in liquid biopsies.

Technical advances over the past two decades have enabled robust detection of cell-free DNA (cfDNA) in biological samples. Yet, higher clinical sensitivity is required to realize the full potential of liquid biopsies. This opinion article argues that to overcome current limitations, the abundance of informative cfDNA molecules - such as circulating tumor DNA (ctDNA) - collected in a sample needs to increase.

Heparan sulfate regulates the fate decisions of human pluripotent stem cells.

Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1 hPSCs maintain self-renewal and pluripotency under standard culture conditions that contain high levels of basic fibroblast growth factor(bFGF), a requirement for sufficient bFGF signaling in the engineered cells.