High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is released during tissue damage from immune and non-immune cells — including microglia and neurons. HMGB1 can contribute to progression of numerous chronic inflammatory and autoimmune diseases which is mediated in part by interaction with the receptor for advanced glycation endproducts (RAGE). There is increasing evidence from in vitro studies that HMGB1 may link the two main pathophysiological components of Parkinson's disease (PD), i.e. progressive dopaminergic degeneration and chronic neuroinflammation which underlie the mechanistic basis of PD progression.Analysis of tissue and biofluid samples from PD patients, showed increased HMGB1 levels in human postmortem substantia nigra specimens as well as in the cerebrospinal fluid and serum of PD patients. In a mouse model of PD induced by sub-acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), systemic administration of neutralizing antibodies to HMGB1 partly inhibited the dopaminergic cell death, and reduced the increase of RAGE and tumour necrosis factor-alpha. The small natural molecule glycyrrhizin, a component from liquorice root which can directly bind to HMGB1, both suppressed MPTP-induced HMGB1 and RAGE upregulation while reducing MPTP-induced dopaminergic cell death in a dose dependent manner.These results provide first in vivo evidence that HMGB1 serves as a powerful bridge between progressive dopaminergic neurodegeneration and chronic neuroinflammation in a model of PD, suggesting that HMGB1 is a suitable target for neuroprotective trials in PD.

Abstract. Proximal methods have recently been shown to provide effective optimization procedures to solve the variational problems defining the 1 regularization algorithms. The goal of the paper is twofold. First we discuss how proximal methods can be applied to solve a large class of machine learning algorithms which can be seen as extensions of 1 regularization, namely structured sparsity regularization. For all these algorithms, it is possible to derive an optimization procedure which corresponds to an iterative projection algorithm. Second, we discuss the effect of a preconditioning of the optimization procedure achieved by adding a strictly convex functional to the objective function. Structured sparsity algorithms are usually based on minimizing a convex (not strictly convex) objective function and this might lead to undesired unstable behavior. We show that by perturbing the objective function by a small strictly convex term we often reduce substantially the number of required computations without affecting the prediction performance of the obtained solution.

Parkinson's disease (PD) is the second most common neurodegenerative disease and results from the loss of dopaminergic neurons of the nigrostriatal pathway. The pathogenesis of PD is poorly understood, but inflammatory processes have been implicated. Indeed increases in the number of major histocompatibility complex II (MHC II) reactive cells have long been recognised in the brains of PD patients at post‐mortem. However whether cells expressing MHC II play an active role in PD pathogenesis has not been delineated. This was addressed utilising a transgenic mouse null for MHC II and the parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). In wild‐type mice MHC II levels in the ventral midbrain were upregulated 1–2 days after MPTP treatment and MHC II was localized in both astrocytes and microglia. MHC II null mice showed significant reductions in MPTP‐induced dopaminergic neuron loss and a significantly reduced invasion of astrocytes and microglia in MHC II null mice receiving MPTP compared with controls. In addition, MHC II null mice failed to show increases in interferon‐γ or tumour necrosis factor‐α in the brain after MPTP treatment, as was found in wild‐type mice. However, interleukin‐1β was significantly increased in both wild‐type and MHC II null mice. These data indicate that in addition to microglial cell/myeloid cell activation MHC Class II‐mediated T cell activation is required for the full expression of pathology in this model of PD. GLIA 2016;64:386–395

The MAGIC-5 Project aims at developing Computer Aided Detection (CAD) software for Medical Applications on distributed databases by means of a GRID Infrastructure Connection. The use of automatic systems for analyzing medical images is of paramount importance in the screening programs, due to the huge amount of data to check. Examples are: mammographies for breast cancer detection, Computed-Tomography (CT) images for lung cancer analysis, and the Positron Emission Tomography (PET) imaging for the early diagnosis of the Alzheimer disease. The need for acquiring and analyzing data stored in different locations requires a GRID approach of distributed computing system and associated data management. The GRID technologies allow remote image analysis and interactive online diagnosis, with a relevant reduction of the delays actually associated to the screening programs. From this point of view, the MAGIC-5 collaboration can be seen as a group of distributed users sharing their resources for implementing different Virtual Organizations (VO), each one aiming at developing screening programs, tele-training, tele-diagnosis and epidemiologic studies for a particular pathology.

A newborn girl with multiple anomalies had an interstitial deletion of the long arm of chromosome 7 (46, XX,der(7)mat). The patient's mother and maternal grandmother were carriers of a balanced translocation, 46,XX, inv ins(5;7)(q14;q3200q2200). Both cytogenetic and clinical findings were similar to those in the two cases already described.