Fragmentation of metastable anions of all deoxynucleosides and nucleosides constituting DNA and RNA has been studied experimentally and by computer simulations. The ions were formed through deprotonation in matrix assisted laser desorption/ionisation (MALDI). Clear difference in fragmentation patterns was obtained for nucleosides containing purine vs. pyrimidine bases. To elucidate the role of ...

High-speed AFM (atomic force microscopy also called scanning force microscopy) provides nanometre spatial resolution and sub-second temporal resolution images of individual molecules. We exploit these features to study diffusion and motor activity of the RAD54 DNA repair factor. Human RAD54 functions at critical steps in recombinational-DNA repair. It is a member of the Swi2/Snf2 family of chro...

The enzyme assay in a femtoliter chamber array is a simple and efficient method for concentrating the reaction product; it greatly improves the detection sensitivity down to the single-molecule level. However, in previous methods, controlling the initiation and termination of the reaction in each chamber is difficult once enclosed. Furthermore, the recovery of the enzyme and product is also dif...

The chemical reactivity of acyl glucuronide (AG) has been thought to be associated with the toxic properties of drugs containing carboxylic acid moieties, but there has been no direct evidence showing that AG formation is related to the observed toxicity. In the present study, the cytotoxicity of AGs, especially that associated with the inflammatory response, was investigated. The changes in th...

Inflammasomes are cytosolic multiprotein complexes that sense microbial infection and trigger cytokine production and cell death. However, the molecular components of inflammasomes and what they sense remain poorly defined. Here we demonstrate that 35 amino acids of the carboxyl terminus of flagellin triggered inflammasome activation in the absence of bacterial contaminants or secretion systems...

The selective forces that played a role in the evolution of the musculoskeletal system of the genus Homo have long been debated and remain poorly understood. In this investigation, we introduce a new approach for testing alternative hypotheses. Our analysis is based on the premise that natural selection can be expected to have resulted in muscles that are large enough to achieve necessary level...

Deeper insight into the molecular pathways that orchestrate skeletal myogenesis should enhance our understanding of, and ability to treat, human skeletal muscle disease. It is now widely appreciated that nutrients, such as molecular oxygen (O2), modulate skeletal muscle formation. During early stages of development and regeneration, skeletalmuscle progenitors reside in lowO2environments before ...

Department of Cognitive, Linguistic & Psychological Sciences, Brown University, Providence, RI 02906; Department of Psychiatry, The University of Texas at Austin, Austin, TX 78712; Department of Psychology, New York University, New York, NY 10003; Department of Psychology, Princeton University, Princeton, NJ; Center for Neural Science, New York University, New York, NY 10003; and Emotional Brai...

Background-—Magnetic resonance imaging of carotid plaque can aid in stroke risk stratification in patients with carotid stenosis. However, the prevalence of complicated carotid plaque in patients with cryptogenic stroke is uncertain, especially as assessed by plaque imaging techniques routinely included in acute stroke magnetic resonance imaging protocols. We assessed whether the magnetic reson...

DISRUPTED-IN-SCHIZOPHRENIA (DISC1) has been one of themost intensively studied genetic risk factors for mental illness since it was discovered throughpositionalmappingofa translocationbreakpoint ina largeScottish family where a balanced chromosomal translocationwas found to segregate with schizophrenia and affective disorders. While the evidence for it being central to disease pathogenesis in t...