3D-PMB is a transperineal biopsy that can be safely used to accurately stage prostate cancer patients. At the present time, when patient management is increasingly based on the extent and characteristics of prostate cancer, 3D-PMB could have a profound effect on patient management.

Apolipoprotein E (APOE) genotype affects outcomes of Alzheimer’s Disease and other conditions of brain damage. Using APOE knock-in mice, we have previously shown that APOE- ε4 Targeted Replacement (TR) mice have fewer dendritic spines and reduced branching in cortical neurons. Since dendritic spines are postsynaptic sites of excitatory neurotransmission, we used APOE TR mice to examine whether APOE genotype affected the various elements of the glutamate-glutamine cycle. We found that levels of glutamine synthetase and glutamate uptake transporters were unchanged among the APOE genotypes. However, compared to APOE- ε3 TR mice, APOE-ε4 TR mice had decreased glutaminase levels (18%, p<0.05), suggesting decreased conversion of glutamine to glutamate. APOE-ε4 TR mice also had increased levels of the vesicular glutamate transporter VGLUT1 (20%, p<0.05), suggesting that APOE genotype affects presynaptic terminal composition. To address whether these changes affected normal neurotransmission, we examined the production and metabolism of glutamate and glutamine at 4–5 months and 1 year. Using high frequency 13C/1H nuclear magnetic resonance (NMR) spectroscopy, we found that APOE-ε4 TR mice have decreased production of glutamate and increased levels of glutamine. These factors may contribute to the increased risk of neurodegeneration associated with APOE-ε4, and also act as surrogate markers for AD risk.

The E3 ubiquitin ligase Parkin plays a central role in the pathogenesis of many neurodegenerative diseases. Parkin promotes specific ubiquitination and affects the localization of TDP-43, which controls the translation of thousands of mRNAs. Here we tested the effects of lentiviral Parkin and TDP-43 expression on amino acid metabolism in the rat motor cortex using high frequency 13C NMR spectroscopy. TDP-43 expression increased glutamate levels, decreased the levels of other amino acids, including glutamine, aspartate, leucine and isoleucine, and impaired mitochondrial TCA cycle. TDP-43 induced lactate accumulation and altered the balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters. Parkin restored amino acid levels, neurotransmitter balance and TCA cycle metabolism, rescuing neurons from TDP-43-induced apoptotic death. Furthermore, TDP-43 expression led to an increase in 4E-BP levels, perhaps altering translational control and deregulating amino acid synthesis; while Parkin reversed the effects of TDP-43 on the 4E-BP signaling pathway. Taken together, these data suggest that Parkin may affect TDP-43 localization and mitigate its effects on 4E-BP signaling and loss of amino acid homeostasis.

The leukotriene A4 hydrolase enzyme is a dual functioning enzyme with the following two catalytic activities: an epoxide hydrolase function that transforms the lipid metabolite leukotriene A4 to leukotriene B4 and an aminopeptidase function that hydrolyzes short peptides. To date, all drug discovery efforts have focused on the epoxide hydrolase activity of the enzyme, because of extensive biological characterization of the pro- inflammatory properties of its metabolite, leukotriene B4. Herein, we have designed a small molecule, 4-methoxydiphenylmethane, as a pharmacological agent that is bioavailable and augments the aminopeptidase activity of the leukotriene A4 hydrolase enzyme. Pre-clinical evaluation of our drug showed protection against intranasal elastase-induced pulmonary emphysema in murine models.