Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

La Relación Entre la Motivación Docente y Variables de la Organización: Revisión de la Literatura

Abstract Teacher motivation plays a central role in education because ofitsimpacton student motivation. Previous reviews of teacher motivation have focused on individual variables and psychopathology indicators. However, it is also important to understand the effect of organizational variableson teacher motivationbecause these highlightthe contextthat the teacher is a part of(i.e.,the school). The literature review in this paper analysed studies related to teacher motivation and a pre-defined group of organizational variablesthat werepublished between 1990 and 2014 in several electronic databases.The study found that organizational culture was the most studied variable associated with teacher motivationand most studies in this area were published between 2010 and 2014.Further,there was a prevalence of quantitative studies. This paper concludes with the theoreticaland practical implications of the results,as well assuggestions for future research directions

MyéLome multiple révélé par deux infections invasives à Streptococcus pneumoniae :À propos d'un cas

We here report the case of a 45-year-old patient who presented 2 invasive infections with Streptococcus Pneumoniae in 9 months period (two bacteriemias, associated with pneumonia then meningitis), in which the workup of a possible immunodeficiency led to the diagnosis of multiple myeloma, an usual pathology at this age. Although S. Pneumoniae infections are a frequent complication of multiple myeloma, they do not usually lead to its diagnosis. The mechanisms of this greater susceptibility to encapsulated germs as S. pneumoniae in multiple myeloma are discussed. In clinical practice, this case reminds us that the occurrence of at least two severe bacterial infections is a criterion to perform a search for immunodeficiency.SCOPUS: ar.jinfo:eu-repo/semantics/publishe