Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator

We report the 1.1-Å resolution crystal structure of a bulky rhodium complex bound to two different DNA sites, mismatched and matched in the oligonucleotide 5'-(dCGGAAATTCCCG)2-3'. At the AC mismatch site, the structure reveals ligand insertion from the minor groove with ejection of both mismatched bases and elucidates how destabilized mispairs in DNA may be recognized. This unique binding mode contrasts with major groove intercalation, observed at a matched site, where doubling of the base pair rise accommodates stacking of the intercalator. Mass spectral analysis reveals different photocleavage products associated with the two binding modes in the crystal, with only products characteristic of mismatch binding in solution. This structure, illustrating two clearly distinct binding modes for a molecule with DNA, provides a rationale for the interrogation and detection of mismatches

Metallo-intercalators and metallo-insertors

Since the elucidation of the structure of double helical DNA, the construction of small molecules that recognize and react at specific DNA sites has been an area of considerable interest. In particular, the study of transition metal complexes that bind DNA with specificity has been a burgeoning field. This growth has been due in large part to the useful properties of metal complexes, which possess a wide array of photophysical attributes and allow for the modular assembly of an ensemble of recognition elements. Here we review recent experiments in our laboratory aimed at the design and study of octahedral metal complexes that bind DNA non-covalently and target reactions to specific sites. Emphasis is placed both on the variety of methods employed to confer site-specificity and upon the many applications for these complexes. Particular attention is given to the family of complexes recently designed that target single base mismatches in duplex DNA through metallo-insertion

Mental Health And The Role Of The States

Researchers from the State Health Care Spending Project -- a collaboration between The Pew Charitable Trusts and the John D. and Catherine T. MacArthur Foundation -- sought to better understand the country's mental health challenges and, in particular, the states' role in addressing them. The project found that:In 2013, approximately 44 million adults -- 18.5 percent of the population 18 and older -- were classified as having a mental illness. Of these, 10 million had a serious mental illness. The rate of serious mental illness varied from state to state.In 2009, the most recent year for which national mental health data are available, $147 billion was spent on mental health treatment in the United States. A majority of the spending, 60 percent, came from public sources such as Medicaid, state and local governments, Medicare, and federal grants. Private sources, including health insurance and individual out-of-pocket spending, made up the difference.Funding from states and localities totaled$22 billion (15 percent) in 2009. This total does not include state and local Medicaid expenditures. Counting those contributions brings total state and local spending up to $35.5 billion (24 percent).This report is intended to help federal, state, and local policymakers working to address the country's mental health challenges to better understand their prevalence, treatment, and funding trends

Eye movement sequences during simple versus complex information processing of scenes in autism spectrum disorder

Minshew and Goldstein (1998) postulated that autism spectrum disorder (ASD) is a disorder of complex information processing. The current study was designed to investigate this hypothesis. Participants with and without ASD completed two scene perception tasks: a simple “spot the difference” task, where they had to say which one of a pair of pictures had a detail missing, and a complex “which one's weird” task, where they had to decide which one of a pair of pictures looks “weird”. Participants with ASD did not differ from TD participants in their ability to accurately identify the target picture in both tasks. However, analysis of the eye movement sequences showed that participants with ASD viewed scenes differently from normal controls exclusively for the complex task. This difference in eye movement patterns, and the method used to examine different patterns, adds to the knowledge base regarding eye movements and ASD. Our results are in accordance with Minshew and Goldstein's theory that complex, but not simple, information processing is impaired in ASD.<br/

Health-Promoting Behaviors and Well Being among Middle-aged and Older Adults

The primary goal of this study was to evaluate the influence of adherence to nutrition guidelines and engaging in regular physical activity on the physical and psychological dimensions of well-being in a sample of middle-aged and older adults. All available sociodemographic indicators were also analyzed in order to investigate potential interactions. A structural equation model was constructed utilizing data from 348 middle-aged and older adults who completed the Health Behavior and Knowledge Survey. Results indicated the model was a good fit to the data, accounting for 40.4% of the variance in physical well-being and 26.3% of variance in psychological well-being. Examination of individual paths within the model indicated complex interactions among variables involved in performance of health-promoting behaviors and in physical and psychological well-being, directly. Indications for future directions are discussed

Developing the Next-Generation Don Draper

Technology and the proliferation of data have transformed the advertising industry. Those with digital and analytical skills are now more employable than those with “traditional” advertising skills. At the same time, colleges and universities face increasing emphasis on job placement rates. Are advertising programs providing students with the skills needed to win jobs today and become successful employees tomorrow? Today’s “next-generation Don Drapers” must be fluent not only in creativity and big ideas but also in analysis and Big Data

The Effect of Varying Levels of Depressive Symptoms on Mindfulness Acquisition: An Exploratory Study

Research and clinical theory increasingly suggest that mindfulness may be an effective clinical intervention for a myriad of mental illnesses. However, there is debate in the field as to whether or not mindfulness-based programs may be beneficial for treatment of active depression. Those cautioning against the use of mindfulness-based programs suggest that the cognitive demands of a meditation practice may be too difficult for those with acute depressive symptoms. The purpose of this study is to investigate whether differences exist between individuals with varying levels of depressive symptoms in the ability to acquire mindfulness skills. Data comes from a two-week, longitudinal study in which undergraduates, with a range of depressive symptoms, engaged in a breath-focused mindfulness exercise every other day. Self-reported trait mindfulness, state mindfulness, depressive symptoms, rumination, and sleep quality were measured at various time points over the two-week study period. Multilevel modeling was used for main analyses. Results suggest individuals with more acute, depressive symptoms may be able to successfully acquire trait mindfulness skills, as well as receive an adjunctive benefit such as a reduction in depressive symptoms over time, and reduced rumination and increased sleep quality. Limitations and future directions are addressed