Abnormal Changes in NKT Cells, the IGF-1 Axis, and Liver Pathology in an Animal Model of ALS

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing fatal neurodegenerative disorder characterized by the selective death of motor neurons (MN) in the spinal cord, and is associated with local neuroinflammation. Circulating CD4+ T cells are required for controlling the local detrimental inflammation in neurodegenerative diseases, and for supporting neuronal survival, including that of MN. T-cell deficiency increases neuronal loss, while boosting T cell levels reduces it. Here, we show that in the mutant superoxide dismutase 1 G93A (mSOD1) mouse model of ALS, the levels of natural killer T (NKT) cells increased dramatically, and T-cell distribution was altered both in lymphoid organs and in the spinal cord relative to wild-type mice. The most significant elevation of NKT cells was observed in the liver, concomitant with organ atrophy. Hepatic expression levels of insulin-like growth factor (IGF)-1 decreased, while the expression of IGF binding protein (IGFBP)-1 was augmented by more than 20-fold in mSOD1 mice relative to wild-type animals. Moreover, hepatic lymphocytes of pre-symptomatic mSOD1 mice were found to secrete significantly higher levels of cytokines when stimulated with an NKT ligand, ex-vivo. Immunomodulation of NKT cells using an analogue of α-galactosyl ceramide (α-GalCer), in a specific regimen, diminished the number of these cells in the periphery, and induced recruitment of T cells into the affected spinal cord, leading to a modest but significant prolongation of life span of mSOD1 mice. These results identify NKT cells as potential players in ALS, and the liver as an additional site of major pathology in this disease, thereby emphasizing that ALS is not only a non-cell autonomous, but a non-tissue autonomous disease, as well. Moreover, the results suggest potential new therapeutic targets such as the liver for immunomodulatory intervention for modifying the disease, in addition to MN-based neuroprotection and systemic treatments aimed at reducing oxidative stress

He Said, She Said : With a Twist

Many studies have explored the effect of judges’ memberships in social categories, such as gender, ethnicity, religion, age, and political affiliation, on their decisions. No study has investigated whether membership in social categories affects public perceptions of judicial decisions, especially when such membership is suspected to affect one’s perception of reality. This question is important, inter alia, because the argument that the judiciary must be representative or reflective of society is partly linked to the assumption that representation enhances public trust in the judiciary. Such an assumption holds to the extent that lack of representation is perceived by members of a particular group as an exclusion of their unique viewpoint. And this may happen because members of different groups (1) truly have different beliefs, values, interests, motivations, and emotional and cognitive processes, or (2) perceive a difference even where none exists. The article focuses on the latter, or, more accurately, on group-based biases in the perception of judgments. The study examines (1) whether male and female judges’ decisions are perceived differently, and (2) whether men and women perceive judgments differently. Specifically, it examines whether identical judgments concerning gender-charged events are perceived differently due to the judge’s gender, the evaluator’s gender, or a combination thereof, indicating the existence of cognitive biases. To do so, we employ an experimental research design. Our two independent variables are the judge’s gender (an active variable) and the evaluator’s gender (an attribute variable). The dependent variables are evaluators’ perceptions with respect to different features of the judgments. The study asks, for example, whether people deem sentences imposed by female judges on sex offenders more severe than identical sentences imposed by male judges, whether women and men perceive identical sentences differently regardless of the judge’s gender, and whether men and women perceive identical sentences imposed on sex offenders as fairer when imposed by judges of their own gender