ITN protection, MSP1 antibody levels and malaria episodes in young children of rural Burkina Faso

Malaria blood-stage vaccines are in an early phase of clinical development with MSP1 being a major antigen candidate. There are limited data on the protective efficacy of antibodies against subunits of MSP1 in the malaria endemic areas of sub-Saharan Africa. This prospective cohort study was nested into a large insecticide-treated mosquito net (ITN) trial during which neonates were individually randomised to ITN protection from birth vs. protection from month six onwards in rural Burkina Faso. A sub sample of 120 children from three villages was followed for 10 months with six measurements of MSP1(42) antibodies (ELISA based on recombinant 42kDa fragment) and daily assessment of malaria episodes. Time to the next malaria episode was determined in relation to MSP1(42) antibody titres. MSP1(42) antibody titres were dependent on age, season, ITN-group, number of previous malaria episodes and parasitaemia. There were no significant differences in time until the next malaria episode in children with low compared to children with high MSP1(42) antibody titres at any point in time (101 vs. 97 days in May, p=0.6; 58 vs. 84 days in September, p=0.3; 144 vs. 161 days in March, p=0.5). The findings of this study support the short-lived nature of the humoral immune response in infants of malaria endemic areas. The study provides no evidence for antibodies against a subunit of MSP1 being protective against new malaria episodes in infants.     

Dysfunction of a Structurally Normal Motor Pathway in a Brain Injury Patient as Revealed by Multimodal Integrated Techniques

We report on a patient with left hemiparesis and peripersonal neglect after post-traumatic left frontal hemorrhage, who underwent fMRI, TMS and TCD to identify the functional abnormalities that account for his neurological symptoms, in the absence of any detectable lesion affecting right motor areas.     

Odor Identification and Self-reported Olfactory Functioning in Patients with Subtypes of Mild Cognitive Impairment

Olfactory dysfunction is a very early symptom of Alzheimer's disease (AD), and olfactory dysfunction has also been found in mild cognitive impairment (MCI). The goal of the present study was to compare odor identification ability and self-reported olfactory functioning in patients with different types of MCI. We included 104 elderly participants classified into two groups: patients with mild cognitive impairment (MCI) and elderly controls (EC). Based on their performance in neuropsychological testing the study population was divided into four groups of participants based on cognitive features: amnestic MCI single domain (11), amnestic MCI multiple domain (19), non-amnestic MCI single domain (21) and non-amnestic MCI multiple domain (13), respectively. The MCI patients were compared to 40 elderly controls (EC) controls with no cognitive deficit. Comparison for odor identification revealed a significant difference between amnestic MCI multiple domain patients and the EC group. No other group comparison was significant. Statistical analyses for self-reported olfactory functioning revealed no significant group differences between any subgroup of MCI patients and the control group. Correlational analyses indicated that odor identification ability was related to cognition whereas no relationship was found for self-reported olfactory functioning. The present study showed that amnestic MCI patients with additional deficits in other cognitive domains have a specific odor identification impairment. Together with cognitive testing, olfactory testing may more accurately help predict whether or not a patient with MCI will convert to AD in the near future.     

Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats

BackgroundVagus nerve stimulation (VNS) has been introduced as a therapeutic option for treatment-resistant depression. The neural and chemical mechanisms responsible for the effects of VNS are largely unclear.MethodsBilateral removal of the olfactory bulbs (OBX) is a validated animal model in depression research. We studied the effects of vagus nerve stimulation (VNS) on disturbed one-way active avoidance learning and neurogenesis in the hippocampal dentate gyrus of rats.ResultsAfter a stimulation period of 3 weeks, OBX rats acquired the learning task as controls. In addition, the OBX-related decrease of neuronal differentiated BrdU positive cells in the dentate gyrus was prevented by VNS.ConclusionsThis suggests that chronic VNS and changes in hippocampal neurogenesis induced by VNS may also account for the amelioration of behavioral deficits in OBX rats. To the best of our knowledge, this is the first report on the restorative effects of VNS on behavioral function in an animal model of depression that can be compared with the effects of antidepressants.     

CD40 interacts directly with RAG1 and RAG2 in autoaggressive T cells and Fas prevents CD40-induced RAG expression

CD4＋ T cells expressing CD40 （Th40 cells） constitute a pathogenic T-cell subset that is necessary and sufficient to transfer autoimmune disease. We have previously demonstrated that CD40 signals peripheral Th40 cells to induce RAG1 and RAG2 expression, proteins necessary for the expression of T-cell receptor （TCR）, leading to TCR revision. The dependency of TCR expression in the thymus on RAG proteins has long been known. However, despite numerous publications, there is controversy as to whether TCR expression can be altered in the periphery, post-thymic selective pressures. Therefore, a better understanding of TCR expression in primary peripheral cells is needed. We now show that the CD40 protein itself interacts with RAG1 and RAG2 as well as with Ku70 and translocates to the nucleus in Th40 cells. This indicates that the CD40 molecule is closely involved in the mechanism of TCR expression in the periphery. In addition, Fas signals act as a silencing mechanism for CD40-induced RAGs and prevent CD40 translocation to the nucleus. It will be important to further understand the involvement of CD40 in peripheral TCR expression and how TCR revision impacts auto-antigen recognition in order to effectively target and tolerize autoaggressive T cells in autoimmune disease.