Membrane-containing virus particles exhibit the mechanics of a composite material for genome protection

The protection of the viral genome during extracellular transport is an absolute requirement for virus survival and replication. In addition to the almost universal proteinaceous capsids, certain viruses add a membrane layer that encloses their double-stranded (ds) DNA genome within the protein shell. Using the membrane-containing enterobacterial virus PRD1 as a prototype, and a combination of nanoindentation assays by atomic force microscopy and finite element modelling, we show that PRD1 provides a greater stability against mechanical stress than that achieved by the majority of dsDNA icosahedral viruses that lack a membrane. We propose that the combination of a stiff and brittle proteinaceous shell coupled with a soft and compliant membrane vesicle yields a tough composite nanomaterial well-suited to protect the viral DNA during extracellular transport

Decentralization in Ukraine and bottom-up European integration

Author´s accepted manuscript.Available from 30/07/2023.acceptedVersio

The Stromal Processing Peptidase of Chloroplasts is Essential in Arabidopsis, with Knockout Mutations Causing Embryo Arrest after the 16-Cell Stage

Stromal processing peptidase (SPP) is a metalloendopeptidase located in the stroma of chloroplasts, and it is responsible for the cleavage of transit peptides from preproteins upon their import into the organelle. Two independent mutant Arabidopsis lines with T-DNA insertions in the SPP gene were analysed (spp-1 and spp-2). For both lines, no homozygous mutant plants could be detected, and the segregating progeny of spp heterozygotes contained heterozygous and wild-type plants in a ratio of 2∶1. The siliques of heterozygous spp-1 and spp-2 plants contained many aborted seeds, at a frequency of ∼25%, suggesting embryo lethality. By contrast, transmission of the spp mutations through the male and female gametes was found to be normal, and so gametophytic effects could be ruled out. To further elucidate the timing of the developmental arrest, mutant and wild-type seeds were cleared and analysed by Nomarski microscopy. A significant proportion (∼25%) of the seeds in mutant siliques exhibited delayed embryogenesis compared to those in wild type. Moreover, the mutant embryos never progressed normally beyond the 16-cell stage, with cell divisions not completing properly thereafter. Heterozygous spp mutant plants were phenotypically indistinguishable from the wild type, indicating that the spp knockout mutations are completely recessive and suggesting that one copy of the SPP gene is able to produce sufficient SPP protein for normal development under standard growth conditions

The Beck Depression Inventory (BDI-II) and a single screening question as screening tools for depressive disorder in Dutch advanced cancer patients

Item does not contain fulltextPURPOSE: Depression is highly prevalent in advanced cancer patients, but the diagnosis of depressive disorder in patients with advanced cancer is difficult. Screening instruments could facilitate diagnosing depressive disorder in patients with advanced cancer. The aim of this study was to determine the validity of the Beck Depression Inventory (BDI-II) and a single screening question as screening tools for depressive disorder in advanced cancer patients. METHODS: Patients with advanced metastatic disease, visiting the outpatient palliative care department, were asked to fill out a self-questionnaire containing the Beck Depression Inventory (BDI-II) and a single screening question "Are you feeling depressed?" The mood section of the PRIME-MD was used as a gold standard. RESULTS: Sixty-one patients with advanced metastatic disease were eligible to be included in the study. Complete data were obtained from 46 patients. The area under the curve of the receiver operating characteristics analysis of the BDI-II was 0.82. The optimal cut-off point of the BDI-II was 16 with a sensitivity of 90% and a specificity of 69%. The single screening question showed a sensitivity of 50% and a specificity of 94%. CONCLUSIONS: The BDI-II seems an adequate screening tool for a depressive disorder in advanced cancer patients. The sensitivity of a single screening question is poor.1 februari 201

Quantitative X-ray Tomography of the Mouse Cochlea

Imaging with hard X-rays allows visualizing cochlear structures while maintaining intrinsic qualities of the tissue, including structure and size. With coherent X-rays, soft tissues, including membranes, can be imaged as well as cells making use of the so-called in-line phase contrast. In the present experiments, partially coherent synchrotron radiation has been used for micro-tomography. Three-dimensional reconstructions of the mouse cochlea have been created using the EM3D software and the volume has been segmented in the Amira Software Suite. The structures that have been reconstructed include scala tympani, scala media, scala vestibuli, Reissner's membrane, basilar membrane, tectorial membrane, organ of Corti, spiral limbus, spiral ganglion and cochlear nerve. Cross-sectional areas of the scalae were measured. The results provide a realistic and quantitative reconstruction of the cochlea

European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR

The Impact of Schistosoma japonicum Infection and Treatment on Ultrasound-Detectable Morbidity: A Five-Year Cohort Study in Southwest China

Schistosomiasis is a water-borne parasite that infects approximately 200 million people worldwide. Schistosoma japonicum, found in Asia, causes disease by releasing eggs in the liver, leading to fibrosis, anemia, and, in children, impaired growth. Ultrasound can assess liver pathology from schistosomiasis; however more information is needed to evaluate the relevance of standard ultrasound measures. We followed 578 people for up to five years, testing for schistosomiasis infection and conducting ultrasound examinations to assess the relationship between infection and seven ultrasound measures and to evaluate the impact of treatment with anti-schistosomiasis chemotherapy (praziquantel) on morbidity. All infections were promptly treated. Fibrosis of the liver parenchyma, pathology unique to S. japonicum, was associated with schistosomiasis infection, and was most advanced in people with high worm burdens. Liver fibrosis declined significantly following treatment, but reversal of severe liver fibrosis was rare. Other ultrasound measures were not consistently related to schistosomiasis infection or treatment. These findings suggest parenchymal fibrosis can be used to measure morbidity attributable to S. japonicum and evaluate the impact of disease control efforts. Because reversal of severe fibrosis was limited, disease control efforts will be most effective if they can not only treat existing infections but also prevent new infections