CD8+ T Cells and IFN-γ Mediate the Time-Dependent Accumulation of Infected Red Blood Cells in Deep Organs during Experimental Cerebral Malaria

Background: Infection with Plasmodium berghei ANKA (PbA) in susceptible mice induces a syndrome called experimental cerebral malaria (ECM) with severe pathologies occurring in various mouse organs. Immune mediators such as T cells or cytokines have been implicated in the pathogenesis of ECM. Red blood cells infected with PbA parasites have been shown to accumulate in the brain and other tissues during infection. This accumulation is thought to be involved in PbA–induced pathologies, which mechanisms are poorly understood. Methods and Findings: Using transgenic PbA parasites expressing the luciferase protein, we have assessed by real-time in vivo imaging the dynamic and temporal contribution of different immune factors in infected red blood cell (IRBC) accumulation and distribution in different organs during PbA infection. Using deficient mice or depleting antibodies, we observed that CD8 + T cells and IFN-c drive the rapid increase in total parasite biomass and accumulation of IRBC in the brain and in different organs 6–12 days post-infection, at a time when mice develop ECM. Other cells types like CD4 + T cells, monocytes or neutrophils or cytokines such as IL-12 and TNF-a did not influence the early increase of total parasite biomass and IRBC accumulation in different organs. Conclusions: CD8 + T cells and IFN-c are the major immune mediators controlling the time-dependent accumulation of P. berghei-infected red blood cells in tissues

GDNF Secreting Human Neural Progenitor Cells Protect Dying Motor Neurons, but Not Their Projection to Muscle, in a Rat Model of Familial ALS

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by rapid loss of muscle control and eventual paralysis due to the death of large motor neurons in the brain and spinal cord. Growth factors such as glial cell line derived neurotrophic factor (GDNF) are known to protect motor neurons from damage in a range of models. However, penetrance through the blood brain barrier and delivery to the spinal cord remains a serious challenge. Although there may be a primary dysfunction in the motor neuron itself, there is also increasing evidence that excitotoxicity due to glial dysfunction plays a crucial role in disease progression. Clearly it would be of great interest if wild type glial cells could ameliorate motor neuron loss in these models, perhaps in combination with the release of growth factors such as GDNF.Human neural progenitor cells can be expanded in culture for long periods and survive transplantation into the adult rodent central nervous system, in some cases making large numbers of GFAP positive astrocytes. They can also be genetically modified to release GDNF (hNPC(GDNF)) and thus act as long-term 'mini pumps' in specific regions of the rodent and primate brain. In the current study we genetically modified human neural stem cells to release GDNF and transplanted them into the spinal cord of rats over-expressing mutant SOD1 (SOD1(G93A)). Following unilateral transplantation into the spinal cord of SOD1(G93A) rats there was robust cellular migration into degenerating areas, efficient delivery of GDNF and remarkable preservation of motor neurons at early and end stages of the disease within chimeric regions. The progenitors retained immature markers, and those not secreting GDNF had no effect on motor neuron survival. Interestingly, this robust motor neuron survival was not accompanied by continued innervation of muscle end plates and thus resulted in no improvement in ipsilateral limb use.The potential to maintain dying motor neurons by delivering GDNF using neural progenitor cells represents a novel and powerful treatment strategy for ALS. While this approach represents a unique way to prevent motor neuron loss, our data also suggest that additional strategies may also be required for maintenance of neuromuscular connections and full functional recovery. However, simply maintaining motor neurons in patients would be the first step of a therapeutic advance for this devastating and incurable disease, while future strategies focus on the maintenance of the neuromuscular junction

Practical considerations for conducting ecotoxicity test methods with manufactured nanomaterials: what have we learnt so far?

This review paper reports the consensus of a technical workshop hosted by the European network, NanoImpactNet (NIN). The workshop aimed to review the collective experience of working at the bench with manufactured nanomaterials (MNMs), and to recommend modifications to existing experimental methods and OECD protocols. Current procedures for cleaning glassware are appropriate for most MNMs, although interference with electrodes may occur. Maintaining exposure is more difficult with MNMs compared to conventional chemicals. A metal salt control is recommended for experiments with metallic MNMs that may release free metal ions. Dispersing agents should be avoided, but if they must be used, then natural or synthetic dispersing agents are possible, and dispersion controls essential. Time constraints and technology gaps indicate that full characterisation of test media during ecotoxicity tests is currently not practical. Details of electron microscopy, dark-field microscopy, a range of spectroscopic methods (EDX, XRD, XANES, EXAFS), light scattering techniques (DLS, SLS) and chromatography are discussed. The development of user-friendly software to predict particle behaviour in test media according to DLVO theory is in progress, and simple optical methods are available to estimate the settling behaviour of suspensions during experiments. However, for soil matrices such simple approaches may not be applicable. Alternatively, a Critical Body Residue approach may be taken in which body concentrations in organisms are related to effects, and toxicity thresholds derived. For microbial assays, the cell wall is a formidable barrier to MNMs and end points that rely on the test substance penetrating the cell may be insensitive. Instead assays based on the cell envelope should be developed for MNMs. In algal growth tests, the abiotic factors that promote particle aggregation in the media (e.g. ionic strength) are also important in providing nutrients, and manipulation of the media to control the dispersion may also inhibit growth. Controls to quantify shading effects, and precise details of lighting regimes, shaking or mixing should be reported in algal tests. Photosynthesis may be more sensitive than traditional growth end points for algae and plants. Tests with invertebrates should consider non-chemical toxicity from particle adherence to the organisms. The use of semi-static exposure methods with fish can reduce the logistical issues of waste water disposal and facilitate aspects of animal husbandry relevant to MMNs. There are concerns that the existing bioaccumulation tests are conceptually flawed for MNMs and that new test(s) are required. In vitro testing strategies, as exemplified by genotoxicity assays, can be modified for MNMs, but the risk of false negatives in some assays is highlighted. In conclusion, most protocols will require some modifications and recommendations are made to aid the researcher at the bench. [Authors]]]> Nanostructures; Toxicity Tests; Ecotoxicology/methods; Guidelines; eng https://serval.unil.ch/resource/serval:BIB_5FCE25CBF6A9.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_5FCE25CBF6A95 info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_5FCE25CBF6A95 info:eu-repo/semantics/submittedVersion info:eu-repo/semantics/openAccess Copying allowed only for non-profit organizations https://serval.unil.ch/disclaimer application/pdf oai:serval.unil.ch:BIB_5FCE8EA1AD9C 2022-02-19T02:22:28Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_5FCE8EA1AD9C Apprendre à suivre une règle : jeux d'alternance et constitution du sujet moral Erard, Y. info:eu-repo/semantics/bookPart incollection 2007 Morale et évolution biologique oai:serval.unil.ch:BIB_5FC219D991AA 2022-02-19T02:22:28Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_5FC219D991AA Réflexion sur la réduction de peine en cas de détention illicite Parein, Loïc info:eu-repo/semantics/article article 2015 Revue de l'avocat, vol. 4, no. 15, pp. 166-170 info:eu-repo/semantics/altIdentifier/pissn/1422-5778 fre https://serval.unil.ch/resource/serval:BIB_5FC219D991AA.P001/REF.pdf info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/restrictedAccess Restricted: indefinite embargo Copying allowed only for non-profit organizations https://serval.unil.ch/disclaimer application/pdf oai:serval.unil.ch:BIB_5FC2874DDD0E 2022-02-19T02:22:28Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_5FC2874DDD0E Radial Ultrasound-Assisted Transbronchial Biopsy: A New Diagnostic Approach for Non-Resolving Pulmonary Infiltrates in Neutropenic Hemato-Oncological Patients. info:doi:10.1007/s00408-016-9947-3 info:eu-repo/semantics/altIdentifier/doi/10.1007/s00408-016-9947-3 info:eu-repo/semantics/altIdentifier/pmid/27704258 Bernasconi, M. Casutt, A. Koutsokera, A. Letovanec, I. Tissot, F. Nicod, L.P. Lovis, A. info:eu-repo/semantics/article article 2016-12 Lung, vol. 194, no. 6, pp. 917-921 info:eu-repo/semantics/altIdentifier/eissn/1432-1750 urn:issn:0341-2040 <![CDATA[The role of radial-endobronchial ultrasound (R-EBUS) assisted transbronchial biopsy (TBB) for the diagnosis of peripheral pulmonary lesions is well established. However, no study has addressed its safety and value in hemato-oncological patients presenting with non-resolving infiltrates during persistent febrile neutropenia. To assess safety and feasibility of R-EBUS assisted TBB in severe thrombocytopenic and neutropenic patients. Over a period of 18 months, eight patients were assessed with R-EBUS assisted TBB after adequate platelet transfusion. This technique allowed precise localisation and sampling of the pulmonary lesions in seven of eight patients. In the seven patients, R-EBUS assisted TBB enabled treatment optimization. Invasive fungal infection was diagnosed in four patients, idiopathic acute fibrinous and organising pneumonia in three patients, and a granulomatous inflammation of undetermined origin in one patient. Importantly, no complications, such as bleeding, were observed. R-EBUS assisted TBB is a promising and safe procedure for the evaluation of nonresolving pulmonary infiltrates in febrile neutropenic hemato-oncological patients