Protein-protein interactions in DNA mismatch repair.

The principal DNA mismatch repair proteins MutS and MutL are versatile enzymes that couple DNA mismatch or damage recognition to other cellular processes. Besides interaction with their DNA substrates this involves transient interactions with other proteins which is triggered by the DNA mismatch or damage and controlled by conformational changes. Both MutS and MutL proteins have ATPase activity, which adds another level to control their activity and interactions with DNA substrates and other proteins. Here we focus on the protein-protein interactions, protein interaction sites and the different levels of structural knowledge about the protein complexes formed with MutS and MutL during the mismatch repair reaction.

Aberrant DNA Methylation of rDNA and PRIMA1 in Borderline Personality Disorder.

Borderline personality disorder (BPD) is a serious psychic disease with a high risk for suicide. DNA methylation is a hallmark for aberrant epigenetic regulation and could be involved in the etiology of BPD. Previously, it has been reported that increased DNA methylation of neuropsychiatric genes is found in the blood of patients with BPD compared to healthy controls. Here, we analyzed DNA methylation patterns of the ribosomal RNA gene (rDNA promoter region and 5'-external transcribed spacer/5'ETS) and the promoter of the proline rich membrane anchor 1 gene (PRIMA1) in peripheral blood samples of 24 female patients (mean age (33 ± 11) years) diagnosed with DSM-IV BPD and in 11 female controls (mean age (32 ± 7) years). A significant aberrant methylation of rDNA and PRIMA1 was revealed for BPD patients using pyrosequencing. For the promoter of PRIMA1, the average methylation of six CpG sites was 1.6-fold higher in BPD patients compared to controls. In contrast, the methylation levels of the rDNA promoter region and the 5'ETS were significantly lower (0.9-fold) in patients with BPD compared to controls. Thus, for nine CpGs located in the rDNA promoter region and for four CpGs at the 5'ETS decreased methylation was found in peripheral blood of patients compared to controls. Our results suggest that aberrant methylation of rDNA and PRIMA1 is associated with the pathogenesis of BPD.

The Integration of Technology into Treatment Programs to Aid in the Reduction of Chronic Pain.

In the United States, roughly $600 billion is spent on pain management - usually in the form of addictive opioid drugs. Due to the dangers associated with long-term opiate-based pain medication, the development of additional strategies for chronic pain management is warranted. The advent of smartphones and associated technology has provided healthcare providers with a unique opportunity to provide pain management support. This review summarizes of the use of technology to supplement chronic pain management regimens. Smartphone and internet-based applications that employ online journals facilitate improved communication between patient and clinician and allow for more personalized care and improved pain management. For instance, the e-Ouch application provides a platform for pain logs as well as feedback and coaching to patients via Twitter postings and blogs. Other applications provide online resources and blogs to improve patient education, which has shown to relieve patient symptoms through lifestyle modification. Internet-delivered cognitive behavioral therapy (CBT) focuses on the psychological coping mechanisms. The application of technology and smartphone apps toward pain management shows promise toward reducing the use of opioids in pain management, but has yet to be incorporated as a standard practice. More robust studies critically evaluating the efficacy of these technology-based therapies need to be conducted before standardization and insurance coverage can become reality.