How Are Adenosine and Adenosine A Receptors Involved in the Pathophysiology of Amyotrophic Lateral Sclerosis?

Adenosine is extensively distributed in the central and peripheral nervous systems, where it plays a key role as a neuromodulator. It has long been implicated in the pathogenesis of progressive neurogenerative disorders such as Parkinson's disease, and there is now growing interest in its role in amyotrophic lateral sclerosis (ALS). The motor neurons affected in ALS are responsive to adenosine receptor function, and there is accumulating evidence for beneficial effects of adenosine A receptor antagonism.

Behavioral Health and Adjustment to College Life for Student Service Members/Veterans.

Objective: Increasing numbers of student service members/veterans (SSM/Vs) are enrolling in college. However, little is known about how their previous military experience affects their adjustment to this new role. The present study tested the hypothesis that SSM/Vs who report adjustment problems in college have a higher incidence of posttraumatic stress disorder (PTSD), depression, and other behavioral health problems compared with those who do not report adjustment problems.

Maternal care, maltreatment and callous-unemotional traits among urban male juvenile offenders.

Callous-unemotional (CU) traits (i.e., lack of empathy/guilt, uncaring attitudes) are believed to be a developmental antecedent to adult psychopathy and identify antisocial youth at risk for severe and persistent aggression.

Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage.

MDM2 is a major regulator of p53 by acting as a ubiquitin E3 ligase. The central acidic domain and C-terminal RING domain of MDM2 are both indispensable for ubiquitination of p53. Our previous study suggested that ATM phosphorylation of MDM2 near the C terminus inhibits RING domain oligomerization, resulting in p53 stabilization after DNA damage.

Inhibition of p53 DNA binding function by the MDM2 protein acidic domain.

MDM2 regulates p53 predominantly by promoting p53 ubiquitination. However, ubiquitination-independent mechanisms of MDM2 have also been implicated. Here we show that MDM2 inhibits p53 DNA binding activity in vitro and in vivo.

Marked aneuploidy and loss of multiple chromosomes are common in autosomal mutants isolated from normal mouse kidney epithelium.

Marked aneuploidy and loss of multiple chromosomes are hallmarks of cancer, but whether these events are only present in malignant cells is not known. In prior work, we showed that approximately half of spontaneous autosomal mutants isolated directly from normal kidney epithelium arose from loss of a marker chromosome 8 containing the wild type Aprt gene. Chromosome loss was detected by loss of heterozygosity (LOH) for all chromosome 8 polymorphic loci examined.

MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output.

MDM2 is a key regulator of the p53 tumor suppressor acting primarily as an E3 ubiquitin ligase to promote its degradation. MDM2 also inhibits p53 transcriptional activity by recruiting histone deacetylase and corepressors to p53. Here, we show that immunopurified MDM2 complexes have significant histone H3-K9 methyltransferase activity.