[Digital media use and sleep of adolescents: the effect of rules at home].

Objective: To test whether parental rules regarding the amount of digital media use is associated with the sleep of Dutch adolescents, and whether this is indirectly due to lower digital media use.

Design: Cross-sectional study METHOD: Adolescents and their parents of the Amsterdam Born Children and their Development (ABCD) study completed questionnaires in 2019 at the age of 15-16 years (n=1369; 56% girls). Parents and adolescents reported whether there are rules regarding the amount of digital media use.

Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models.

CD3 bispecific antibodies (bsAbs) show great promise as anticancer therapeutics. Here, we show in-depth mechanistic studies of a CD3 bsAb in solid cancer, using DuoBody-CD3x5T4. Cross-linking T cells with tumor cells expressing the oncofetal antigen 5T4 was required to induce cytotoxicity.

Assessment of occupational exposure to nebulized isopropyl alcohol as disinfectant during aseptic compounding of parenteral cytotoxic drugs in cleanrooms.

Pharmacy technicians are exposed to volatile organic compounds, like the disinfectant isopropyl alcohol (IPA), during the process of aseptic compounding of parenteral cytotoxic drugs. The occupational exposure to nebulized IPA during aseptic compounding has not been investigated. The aim of this study was to investigate the exposure to IPA during aseptic compounding of parenteral cytotoxic drugs and to assess compliance with legal and regulatory limits.

Meddling with Fate: The Proteasomal Deubiquitinating Enzymes.

Three deubiquitinating enzymes-Rpn11, Usp14, and Uch37-are associated with the proteasome regulatory particle. These enzymes allow proteasomes to remove ubiquitin from substrates before they are translocated into the core particle to be degraded. Although the translocation channel is too narrow for folded proteins, the force of translocation unfolds them mechanically.

Betacoronavirus Adaptation to Humans Involved Progressive Loss of Hemagglutinin-Esterase Lectin Activity.

Human beta1-coronavirus (β1CoV) OC43 emerged relatively recently through a single zoonotic introduction. Like related animal β1CoVs, OC43 uses 9-O-acetylated sialic acid as receptor determinant. β1CoV receptor binding is typically controlled by attachment/fusion spike protein S and receptor-binding/receptor-destroying hemagglutinin-esterase protein HE.

Open-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation.

When in the closed form, the substrate translocation channel of the proteasome core particle (CP) is blocked by the convergent N termini of α-subunits. To probe the role of channel gating in mammalian proteasomes, we deleted the N-terminal tail of α3; the resulting α3ΔN proteasomes are intact but hyperactive in the hydrolysis of fluorogenic peptide substrates and the degradation of polyubiquitinated proteins. Cells expressing the hyperactive proteasomes show markedly elevated degradation of many established proteasome substrates and resistance to oxidative stress.

Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins.

Sialic acids (Sias), 9-carbon-backbone sugars, are among the most complex and versatile molecules of life. As terminal residues of glycans on proteins and lipids, Sias are key elements of glycotopes of both cellular and microbial lectins and thus act as important molecular tags in cell recognition and signaling events. Their functions in such interactions can be regulated by post-synthetic modifications, the most common of which is differential Sia-O-acetylation (O-Ac-Sias).

Granzyme M: behind enemy lines.

The granule-exocytosis pathway is the major mechanism via which cytotoxic lymphocytes eliminate virus-infected and tumor cells. In this pathway, cytotoxic lymphocytes release granules containing the pore-forming protein perforin and a family of serine proteases known as granzymes into the immunological synapse. Pore-formation by perforin facilitates entry of granzymes into the target cell, where they can activate various (death) pathways.

A preliminary comparison of three dermal exposure sampling methods: rinses, wipes and cotton gloves.

Several methods exist to estimate dermal exposure and it is unclear how comparable they are. These methods fall into three main categories: (i) removal techniques (such as wiping or rinsing); (ii) interception techniques (such as gloves, patches, or coveralls); and (iii) fluorescent tracer techniques. Controlled experiments were conducted to compare two removal methods for exposure to particulate, and a removal method with an interception method for exposure to liquids.

Granzyme M targets topoisomerase II alpha to trigger cell cycle arrest and caspase-dependent apoptosis.

Cytotoxic lymphocyte protease granzyme M (GrM) is a potent inducer of tumor cell death. The apoptotic phenotype and mechanism by which it induces cell death, however, remain poorly understood and controversial. Here, we show that GrM-induced cell death was largely caspase-dependent with various hallmarks of classical apoptosis, coinciding with caspase-independent G2/M cell cycle arrest.

Properties of liquids and dusts: how do they influence dermal loading during immersion, deposition, and surface contact exposure pathways?

Background: Although dustiness and viscosity are potential determinants of dermal exposure, their effect on exposure is poorly understood. The goal of this study was to investigate the effect of dustiness and viscosity on dermal exposure by each of three dermal exposure pathways (deposition, surface contact, and immersion).

Methods: The hands of four volunteers were exposed to non-toxic substances: particulate with varying dustiness (calcium acetate, zinc oxide, and Epsom salt) and liquids of varying viscosity (three glycerol/water solutions containing 20, 50, or 85% glycerol) by each pathway.

Granzyme M targets host cell hnRNP K that is essential for human cytomegalovirus replication.

Human cytomegalovirus (HCMV) is the most frequent viral cause of congenital defects and HCMV infection in immunocompromised patients may trigger devastating disease. Cytotoxic lymphocytes control HCMV by releasing granzymes towards virus-infected cells. In mice, granzyme M (GrM) has a physiological role in controlling murine CMV infection.

Hormesis and Cellular Quality Control: A Possible Explanation for the Molecular Mechanisms that Underlie the Benefits of Mild Stress.

In contrast to the detrimental action of severe stress conditions, the beneficial effects of mild stress, known as hormesis, is increasingly discussed and studied. A variety of applications for hormesis in risk assessment processes, anti-ageing strategies and clinical therapies have been proposed. The molecular mechanisms underlying the phenomenon of hormesis, however, are not yet fully understood.

Intracellular serine protease inhibitor SERPINB4 inhibits granzyme M-induced cell death.

Granzyme-mediated cell death is the major pathway for cytotoxic lymphocytes to kill virus-infected and tumor cells. In humans, five different granzymes (i.e.

Human and mouse granzyme M display divergent and species-specific substrate specificities.

Cytotoxic lymphocyte protease GrM (granzyme M) is a potent inducer of tumour cell death and a key regulator of inflammation. Although hGrM (human GrM) and mGrM (mouse GrM) display extensive sequence homology, the substrate specificity of mGrM remains unknown. In the present study, we show that hGrM and mGrM have diverged during evolution.

Proteomic profiling of proteases: tools for granzyme degradomics.

Proteases are a family of proteolytically active enzymes whose dysfunction is implicated in a wide variety of human diseases. Although an estimated 2% of the human genome encodes for proteases, only a small fraction of these enzymes have well-characterized functions. Identification of the specificity and natural substrates of proteases in complex biological samples is challenging, but proteomic screens for proteases are currently experiencing impressive progress.

Isolated abducens nerve palsy after closed head trauma: a pediatric case report.

Cranial nerve lessions often accompany head trauma. Nevertheless, isolated involvement of the sixth nerve without any cranial or cervical fracture is rare. Nerve injury could occur at the sites of the dural entry points and at the petrous apex during down- or upward movement of the brain caused by violent linear force to the head.