Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson’s disease

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder afflicting 2% of the population older than 65 years worldwide. Recently, brain organotypic slices have been used to model neurodegenerative disorders, including PD. They conserve brain three-dimensional architecture, synaptic connectivity and its microenvironment. This model has allowed researchers a simple and rapid method to observe cellular interactions and mechanisms. In the present study, we developed an organotypic PD model from rat brains that includes all the areas involved in the nigrostriatal pathway in a single slice preparation, without using neurotoxins to induce the dopaminergic lesion. The mechanical transection of the nigrostriatal pathway obtained during slice preparation induced PD-like histopathology. Progressive nigrostriatal degeneration was monitored combining innovative approaches, such as diffusion tensor magnetic resonance imaging (DT-RMI) to follow fiber degeneration and mass spectrometry to quantify striatal dopamine content, together with bright-field and fluorescence microscopy imaging. A substantia nigra dopaminergic cell number decrease was observed by immunohistochemistry against rat tyrosine hydroxylase (TH) reaching 80% after 2 days in culture associated with a 30% decrease of striatal TH-positive fiber density, a 15% loss of striatal dopamine content quantified by mass spectrometry and a 70% reduction of nigrostriatal fiber fractional anisotropy quantified by DT-RMI. In addition, a significant decline of medium spiny neuron density was observed from days 7 to 16. These sagittal organotypic slices could be used to study the early stage of PD, namely dopaminergic degeneration, and the late stage of the pathology with dopaminergic and GABAergic neuron loss. This novel model might improve the understanding of PD and may represent a promising tool to refine the evaluation of new therapeutic approaches

The Lisbon patient: Exceptional longevity with HIV suggests healthy aging as an ultimate goal for HIV care

In the context of global aging, HIV infection has become a new chronic disease and requires innovative models of care. Treating isolated comorbidities represents a useless and potentially harmful practice at advanced age. Therefore, a patient-centered approach, in which the interventions are focused on the biology and function of the individual, with understanding of the importance of securing social and home environment that provides psychosocial support, better suits unmet health needs. We present a paradigmatic case of healthy aging: the first reported HIV-infected patient who achieved 100th of life - the Lisbon patient. The construct of healthy aging, recently introduced by the World Health Organization, is the best example of this comprehensive model and could represent the fourth target of UNAIDS agenda of the end of AIDS

Adoptive immunotherapy monitored by micro-MRI in experimental colorectal liver metastasis

In this study we used the colon carcinoma DHDK12 cell line and generated single metastasis after subcapsular injection in BDIX rats as an experimental tumor model. The aim of the work was to set up in vitro experimental conditions to prepare immune effector cells and in vivo conditions for monitoring the effects of such cells injected as adoptive immunotherapy. Dendritic cells can process tumor cell antigens, induce a T-cell response and be used ex vivo to prepare activated lymphocytes. Lymphocytes were harvested from mesenteric lymph nodes and cocultured with bone marrow-derived autologous dendritic cells previously loaded with irradiated tumor cells. In vitro, the coculture: 1) induced the proliferation of lymphocytes, 2) expanded a preferential subpopulation of T CD8 lymphocytes, and 3) was in favor of lymphocyte cytotoxic activity against the DHDK12 tumor cell line. Activated lymphocytes were injected in the tumor-bearing rat portal vein. Parameters could be set to monitor tumor volume by micro MRI. This monitoring before and after treatment and immunohistochemical examinations revealed that: 1) micro MRI is an appropriate tool to survey metastasis growth in rat, 2) injected lymphocytes increase lesional infiltration with T CD8 cells even 15 days after treatment, 3) a dose of 50 millions lymphocytes is not sufficient to act on the course of the tumor

A roadmap for China to peak carbon dioxide emissions and achieve a 20% share of non-fossil fuels in primary energy by 2030

As part of its Paris Agreement commitment, China pledged to peak carbon dioxide (CO2) emissions around 2030, striving to peak earlier, and to increase the non-fossil share of primary energy to 20% by 2030. Yet by the end of 2017, China emitted 28% of the world's energy-related CO2 emissions, 76% of which were from coal use. How China can reinvent its energy economy cost-effectively while still achieving its commitments was the focus of a three-year joint research project completed in September 2016. Overall, this analysis found that if China follows a pathway in which it aggressively adopts all cost-effective energy efficiency and CO2 emission reduction technologies while also aggressively moving away from fossil fuels to renewable and other non-fossil resources, it is possible to not only meet its Paris Agreement Nationally Determined Contribution (NDC) commitments, but also to reduce its 2050 CO2 emissions to a level that is 42% below the country's 2010 CO2 emissions. While numerous barriers exist that will need to be addressed through effective policies and programs in order to realize these potential energy use and emissions reductions, there are also significant local environmental (e.g., air quality), national and global environmental (e.g., mitigation of climate change), human health, and other unquantified benefits that will be realized if this pathway is pursued in China

Search for Higgs bosons decaying into new spin-0 or spin-1 particles in four-lepton final states with the ATLAS detector with 139 fb−1 of pp collision data at √s = 13 TeV

Searches are conducted for new spin-0 or spin-1 bosons using events where a Higgs boson with mass 125 GeV decays into four leptons (ℓ = e, μ). This decay is presumed to occur via an intermediate state which contains two on-shell, promptly decaying bosons: H → XX/ZX → 4ℓ, where the new boson X has a mass between 1 and 60 GeV. The search uses pp collision data collected with the ATLAS detector at the LHC with an integrated luminosity of 139 fb−1 at a centre-of-mass energy s√ = 13 TeV. The data are found to be consistent with Standard Model expectations. Limits are set on fiducial cross sections and on the branching ratio of the Higgs boson to decay into XX/ZX, improving those from previous publications by a factor between two and four. Limits are also set on mixing parameters relevant in extensions of the Standard Model containing a dark sector where X is interpreted to be a dark boson

Is magnetic resonance imaging texture analysis a useful tool for cell therapy in vivo monitoring?

Assessment of anti-tumor treatment efficiency is usually done by measuring tumor size. Treatment may however induce changes in the tumor other than tumor size. Magnetic Resonance Imaging Texture Analysis (MRI-TA) is presently used to follow activated lymphocyte cell therapy. We used a 7T microimager to acquire high-resolution MR images of an experimental liver metastasis from colon carcinoma in rats treated (n = 4) or not (n = 3) with a cell therapy product. MRI-TA was then performed with Linear Discriminant Analysis and showed: i) a significant variation of tumor texture with tumor growth and ii) a significant modification in the texture of tumors treated with activated lymphocytes compared with untreated tumors. T2-weighted images or volume calculation did not evidence any difference. MRI-TA appears as a promising method for early detection and follow-up of response to cell therapy