Crystal structure of vancomycin bound to the resistance determinant D-alanine-D-serine.

Vancomycin is a glycopeptide antibiotic that for decades has been a mainstay of treatment for persistent bacterial infections. However, the spread of antibiotic resistance threatens its continued utility. In particular, vancomycin-resistant enterococci (VRE) have become a pressing clinical challenge. Vancomycin acts by binding and sequestering the intermediate Lipid II in cell-wall biosynthesis, specifically recognizing a D-alanine-D-alanine dipeptide motif within the Lipid II molecule. VRE achieve resistance by remodeling this motif to either D-alanine-D-lactate or D-alanine-D-serine; the former substitution essentially abolishes recognition by vancomycin of Lipid II, whereas the latter reduces the affinity of the antibiotic by roughly one order of magnitude. The complex of vancomycin bound to D-alanine-D-serine has been crystallized, and its 1.20 ŠX-ray crystal structure is presented here. This structure reveals that the D-alanine-D-serine ligand is bound in essentially the same position and same pose as the native D-alanine-D-alanine ligand. The serine-containing ligand appears to be slightly too large to be comfortably accommodated in this way, suggesting one possible contribution to the reduced binding affinity. In addition, two flexible hydroxyl groups - one from the serine side chain of the ligand, and the other from a glucose sugar on the antibiotic - are locked into single conformations in the complex, which is likely to contribute an unfavorable entropic component to the recognition of the serine-containing ligand.

A Comprehensive Evaluation of a Lifelong Learning Program: Program 60.

Lifelong learning programs meet older adults' educational needs and further support their health and well-being leading to more successful aging. In particular, university-based lifelong learning programs have provided older adults with opportunities to not only develop skills and knowledge but also expand new social networks with people of different ages. This study evaluated a university-based lifelong learning program, Program 60, to identify the relationships between participants' experiences in the program and their quality of life. An online survey was employed, and 107 participants completed the self-report survey. The participants reported that classes helped increase their emotional satisfaction and that they enjoyed taking classes with younger students. Their experiences in the program reliably predicted psychological and social elements of their quality of life ( p = .004 and p = .019, respectively). Study results provide helpful information for the development of lifelong learning programs that are responsive to the increasing demands of older adults.

Korean Survivors of the Japanese "Comfort Women" System: Understanding the Lifelong Consequences of Early Life Trauma.

Prior to and during World War II, thousands of girls and young women were abducted from Korea and forced into sexual slavery by the Japanese government. Termed comfort women, these girls and young women suffered extreme sexual, physical, and emotional abuse and trauma. Research on this group is not well-developed and people know little of the impact of this early life trauma on the lives of these women who are now in later life. Using snowball sampling, 16 older adult survivors of the comfort women system participated in semistructured qualitative interviews. Thematic analysis was conducted to gain an understanding of the trauma that these women suffered and how it impacted their lives. Results revealed the depths of the abuse these women suffered, including repeated rapes, physical beatings, humiliation, forced surgery and sterilization, and social exclusion. These early traumatic experiences appeared to reverberate throughout their lives in their family relations, their inability to marry and to conceive children, and their emotional and physical well-being throughout the life course and into later life. The experiences of these survivors illustrate the lasting impact of early-life trauma and can guide interventions with current survivors of sexual abuse or trafficking.

Heterogeneity within adult day services: a focus on centers that serve younger adults with intellectual and developmental disabilities.

As the population of younger adults with intellectual and developmental disabilities continues to grow, adult day services is positioned to be a key provider of community-based care and support. In this article, researchers examine how adult day centers that serve younger adults with intellectual and developmental disabilities differ from centers that serve older and mixed age groups. One-way analyses of variance and post hoc analyses of 490 adult day services centers (N = 490) revealed significant differences in terms of participant, staffing, and organizational characteristics. These findings have important implications for service providers, researchers, and policy makers.