Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

Do Femtonewton Forces Affect Genetic Function? A Review

Protein-Mediated DNA looping is intricately related to gene expression. Therefore any mechanical constraint that disrupts loop formation can play a significant role in gene regulation. Polymer physics models predict that less than a piconewton of force may be sufficient to prevent the formation of DNA loops. Thus, it appears that tension can act as a molecular switch that controls the much larger forces associated with the processive motion of RNA polymerase. Since RNAP can exert forces over 20 pN before it stalls, a ‘substrate tension switch’ could offer a force advantage of two orders of magnitude. Evidence for such a mechanism is seen in recent in vitro micromanipulation experiments. In this article we provide new perspective on existing theory and experimental data on DNA looping in vitro and in vivo . We elaborate on the connection between tension and a variety of other intracellular mechanical constraints including sequence specific curvature and supercoiling. In the process, we emphasize that the richness and versatility of DNA mechanics opens up a whole new paradigm of gene regulation to explore.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41816/1/10867_2005_Article_9002.pd

The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 1 – blood pressure measurement, diagnosis and assessment of risk

All recommendations were graded according to strength of the evidence and were voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here received at least 70% consensus. These guidelines will continue to be updated annually

Systems Engineering of the Psyche Payload

The Psyche mission is a journey to a unique metal asteroid of the same name, (16) Psyche, orbiting the Sun between Mars and Jupiter. Psyche launched October 13th, 2023 from Kennedy Space Center. The mission seeks to answer questions about the formation of planets and explore what may be an exposed nickel-iron core of an early planetesimal, similar to the one hidden at the center of our own Earth. The mission is led by Arizona State University. NASA's Jet Propulsion Laboratory is responsible for mission management, systems engineering, operations, navigation, and some subsystems including command and data handling and telecommunications. This paper focuses on the Psyche Payload System, which consists of a multispectral Imager, a Magnetometer, a Gamma-Ray and Neutron Spectrometer (GRNS), and a Deep Space Optical Communications (DSOC) experiment. The GRNS will measure the asteroid's composition, the Magnetometer will determine whether Psyche is a core by measuring any remnant magnetic field, and the Imager will map its surface and characterize its topography. DSOC is a technology demonstration hosted by the Psyche spacecraft and intended to pave the way for low-power/high-bandwidth communications in deep space using individual photons to encode and transmit information. This paper focuses on the Payload development efforts and key systems engineering processes that made it possible including requirements development, risk reduction activities, key challenges and anomalies, verification and validation, and the final stretch to launch during assembly and test with the integrated spacecraft.</p

The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: part I - blood pressure measurement, diagnosis and assessment of risk

All recommendations were graded according to strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. To be approved, all recommendations were required to be supported by at least 70% of task force members. These guidelines will continue to be updated annually