Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis

Acknowledgements: The authors would like to acknowledge Fraser P. Coxon and Ian Ganley for providing LC3-GFP-mCherry BMDMs. M.S.G. was supported by an FEMS research grant and F.L.v.d.V. was supported by ZonMW under the name EURO-CMC frame of E-Rare-2, the ERA-Net for Research on Rare Diseases.Peer reviewedPublisher PD

Plasma from septic shock patients induces loss of muscle protein

Contains fulltext : 97225.pdf (publisher's version ) (Open Access

Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity

Pancreatic β-cell failure is a critical event in the onset of both main types of diabetes mellitus but underlying mechanisms are not fully understood. β-cells have low anti-oxidant capacity, making them more susceptible to oxidative stress. In type 1 diabetes (T1D), reactive oxygen species (ROS) are associated with pro-inflammatory conditions at the onset of the disease. Here, we investigated the effects of hydrogen peroxide-induced oxidative stress on human β-cells. We show that primary human β-cell function is decreased. This reduced function is associated with an ER stress response and the shuttling of FOXO1 to the nucleus. Furthermore, oxidative stress leads to loss of β-cell maturity genes MAFA and PDX1, and to a concomitant increase in progenitor marker expression of SOX9 and HES1. Overall, we propose that oxidative stress-induced β-cell failure may result from partial dedifferentiation. Targeting antioxidant mechanisms may preserve functional β-cell mass in early stages of development of T1D

Single-cell transcriptomics links loss of human pancreatic β-cell identity to er stress

The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of β-cell maturity genes. Collectively, our findings illus-trate the close relationship between endoplasmic reticulum homeostasis and β-cell phenotype, and strengthen the concept of altered β-cell identity as a mechanism underlying the loss of functional β-cell mass

Feasibility of a classification system for physical therapy, occupational therapy, and sports therapy interventions for mobility and self-care in spinal cord injury rehabilitation

Objective: To test the feasibility of a classification system developed to record the contents of treatment sessions intended to improve mobility and self-care by persons with a spinal cord injury (SCI) in clinical rehabilitation. Design: Descriptive study. Setting: Three Dutch SCI facilities. Participants: Participants (N = 36) as well as physical therapists (n = 20), occupational therapists (n = 14), and sports therapists (n = 2). Interventions: Not applicable. Main Outcome Measures: Questionnaires to assess the clarity of the classification system, time needed to record 1 treatment session, and the distribution of categories and interventions. The classification system consisted of 28 categories at 3 levels of functioning: basic functions (eg, muscle power), basic activities (eg, transfers), and complex activities (eg, walking and moving around outside). Results: Therapists used 1625 codes to record 856 treatment sessions of 142 patients. For 93% of the treatment sessions, the coding caused little or no doubt. The therapists were able to classify 86.3% of the treatment sessions within 3 minutes. The classification system was rated as useful and easy to use. Conclusions: The findings support the suitability of our classification system as a tool to record the contents of SCI treatment sessions in different settings and by different therapists

Structure-Activity Relationship Studies on (R)-PFI-2 Analogues as Inhibitors of Histone Lysine Methyltransferase SETD7

Contains fulltext : 193974.pdf (Publisher’s version ) (Open Access

Single-cell transcriptomics links loss of human pancreatic β-cell identity to er stress

The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of β-cell maturity genes. Collectively, our findings illus-trate the close relationship between endoplasmic reticulum homeostasis and β-cell phenotype, and strengthen the concept of altered β-cell identity as a mechanism underlying the loss of functional β-cell mass.Pattern Recognition and Bioinformatic

Immediate treatment vs. active-surveillance in very-low-risk prostate cancer: the role of patient-, tumour-, and hospital-related factors

Background: To provide insight in the treatment variation of very-low-risk prostate cancer patients and to assess the role of hospital-related factors. Methods: All patients diagnosed with very-low-risk prostate cancer (cT1c-cT2a, PSA < 10 ng/ml, Gleason score <7 and <3 positive cores) in 2015 and 2016 were identified through the population-based Netherlands Cancer Registry. Multilevel logistic regression analyses were performed to examine the crude and case-mix adjusted probability of immediate treatment vs. active-surveillance (AS) according to hospital of diagnosis and to evaluate the effect of patient-, tumour-, and hospital-related factors. Results: In all, 2047 (85.4%) of the 2396 patients with very-low-risk prostate cancer were managed with AS. The crude proportion of patients with AS varied from 33.3 to 100% between hospitals. Case-mix adjusted probability varied from 71 to 97%. Tumour stage cT2a vs. cT1c (OR 2.0, 95%CI 1.1−3.6), two vs. one positive core (OR 2.8, 95%CI 1.6−4.7), diagnostic MRI (OR 2.8, 95%CI 1.5−5.2), discussion of a patient in a multi-disciplinary team (OR 2.2, 95%CI 1.1−4.5), discussion of treatment options with the patient (OR 3.3, 95%CI 1.5−7.4) and type of hospital (non-university referral hospital vs. community hospital: OR 0.5, 95%CI 0.2−0.9) were associated with immediate treatment. Conclusion: The majority of Dutch very-low-risk prostate cancer patients is managed with AS but variation between hospitals exists. Part of the variation is explained by patient- and tumour characteristics but also hospital-related factors play a role. This implies that clinical practice could be improved

Macrophage imaging in central nervous system and in carotid atherosclerotic plaque using ultrasmall superparamagnetic iron oxide in magnetic resonance imaging

SCOPUS: re.jinfo:eu-repo/semantics/publishe