Computationally Modelling Cholesterol Metabolism and Atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death globally. The underlying pathological driver of CVD is atherosclerosis. The primary risk factor for atherosclerosis is elevated low-density lipoprotein cholesterol (LDL-C). Dysregulation of cholesterol metabolism is synonymous with a rise in LDL-C. Due to the complexity of cholesterol metabolism and atherosclerosis mathematical models are routinely used to explore their non-trivial dynamics. Mathematical modelling has generated a wealth of useful biological insights, which have deepened our understanding of these processes. To date however, no model has been developed which fully captures how whole-body cholesterol metabolism intersects with atherosclerosis. The main reason for this is one of scale. Whole body cholesterol metabolism is defined by macroscale physiological processes, while atherosclerosis operates mainly at a microscale. This work describes how a model of cholesterol metabolism was combined with a model of atherosclerotic plaque formation. This new model is capable of reproducing the output from its parent models. Using the new model, we demonstrate how this system can be utilized to identify interventions that lower LDL-C and abrogate plaque formation

Community and Clinical Epidemiology of Borderline Personality Disorder

Several studies of the prevalence of Borderline Personality Disorder (BPD) in community and clinical settings have been carried out to date. Although results vary according to sampling method and assessment method, median point prevalence of BPD is roughly 1%, with higher or lower rates in certain community subpopulations. In clinical settings, BPD prevalence is around 10-12% in outpatient psychiatric clinics and 20-22% among inpatient clinics. Further research is needed to identify the prevalence and correlates of BPD in other clinical settings (e.g., primary care) and to investigate the impact of demographic variables on BPD prevalence

Forest management and wildfire risk in inland northwest

This brief reports the results of a mail survey of forest landowners in northeastern Oregon conducted in the fall of 2012 by the Communities and Forests in Oregon (CAFOR) Project at the University of Colorado and the University of New Hampshire in cooperation with Oregon State University College of Forestry Extension. The mail survey--a follow-up to a telephone survey conducted for the counties of Baker, Union, and Wallowa in the fall of 2011 -was administered to understand who constituted forest landowners in these three coun¬ties and their perceptions about forest management on both public and private land, as well as risks to forests in the area and the actions they have taken to reduce those risks. The respondents indicated that they perceive wildfire as the greatest threat to their lands, and they consider cooperation with neighbors as very or extremely important for land management. Forest landowners believe public lands are managed poorly and see a greater risk of wildfire occurring on neighboring public land than on their own land. Their opinions on land management are not strongly related to background factors or ideology (for example, gender, age, political party, wealth) but may be heavily influenced by personal experience with wildfire

Translational control of the SigR-directed oxidative stress response in streptomyces via IF3-mediated repression of a noncanonical GTC start codon

The major oxidative stress response in Streptomyces is controlled by the sigma factor SigR and its cognate antisigma factor RsrA, and SigR activity is tightly controlled through multiple mechanisms at both the transcriptional and posttranslational levels. Here we show that sigR has a highly unusual GTC start codon and that this leads to another level of SigR regulation, in which SigR translation is repressed by translation initiation factor 3 (IF3). Changing the GTC to a canonical start codon causes SigR to be overproduced relative to RsrA, resulting in unregulated and constitutive expression of the SigR regulon. Similarly, introducing IF3* mutations that impair its ability to repress SigR translation has the same effect. Thus, the noncanonical GTC sigR start codon and its repression by IF3 are critical for the correct and proper functioning of the oxidative stress regulatory system. sigR and rsrA are cotranscribed and translationally coupled, and it had therefore been assumed that SigR and RsrA are produced in stoichiometric amounts. Here we show that RsrA can be transcribed and translated independently of SigR, present evidence that RsrA is normally produced in excess of SigR, and describe the factors that determine SigR-RsrA stoichiometry.IMPORTANCE In all sigma factor-antisigma factor regulatory switches, the relative abundance of the two proteins is critical to the proper functioning of the system. Many sigma-antisigma operons are cotranscribed and translationally coupled, leading to a generic assumption that the sigma and antisigma factors are produced in a fixed 1:1 ratio. In the case of sigR-rsrA, we show instead that the antisigma factor is produced in excess over the sigma factor, providing a buffer to prevent spurious release of sigma activity. This excess arises in part because sigR has an extremely rare noncanonical GTC start codon, and as a result, SigR translation initiation is repressed by IF3. This finding highlights the potential significance of noncanonical start codons, very few of which have been characterized experimentally. It also emphasizes the limitations of predicting start codons using bioinformatic approaches, which rely heavily on the assumption that ATG, GTG, and TTG are the only permissible start codons

The impact of multisensory integration deficits on speech perception in children with autism spectrum disorders.

Speech perception is an inherently multisensory process. When having a face-to-face conversation, a listener not only hears what a speaker is saying, but also sees the articulatory gestures that accompany those sounds. Speech signals in visual and auditory modalities provide complementary information to the listener (Kavanagh and Mattingly, 1974), and when both are perceived in unison, behavioral gains in in speech perception are observed (Sumby and Pollack, 1954). Notably, this benefit is accentuated when speech is perceived in a noisy environment (Sumby and Pollack, 1954). To achieve a behavioral gain from multisensory processing of speech, however, the auditory and visual signals must be perceptually bound into a single, unified percept. The most commonly cited effect that demonstrates perceptual binding in audiovisual speech perception is the McGurk effect (McGurk and MacDonald, 1976), where a listener hears a speaker utter the syllable “ba,” and sees the speaker utter the syllable “ga.” When these two speech signals are perceptually bound, the listener perceives the speaker as having said “da” or “tha,” syllables that are not contained in either of the unisensory signals, resulting in a perceptual binding, or integration, of the speech signals (Calvert and Thesen, 2004)

Beagle 2: Seeking the signatures of life on Mars

ESA's Beagle 2 lander will land on Mars to search for signatures of present and past life. A Gas Analysis Package (GAP) with a mass spectrometer, XRF, Mossbauer, stereo cameras, microscope, environmental sensors, rock corer/grinder, and a Mole attachment are on the lander

Are We There Yet?: The Development of a Corpus Annotated for Social Acts in Multilingual Online Discourse

We present the AAWD and AACD corpora, a collection of discussions drawn from Wikipedia talk pages and small group IRC discussions in English, Russian and Mandarin. Our datasets are annotated with labels capturing two kinds of social acts: alignment moves and authority claims. We describe these social acts, describe our annotation process, highlight challenges we encountered and strategies we employed during annotation, and present some analyses of resulting data set which illustrate the utility of our corpus and identify interactions among social acts and between participant status and social acts and in online discourse

Nanoscale-length control of the flagellar driveshaft requires hitting the tethered outer membrane

The bacterial flagellum exemplifies a system where even small deviations from the highly regulated flagellar assembly process can abolish motility and cause negative physiological outcomes. Consequently, bacteria have evolved elegant and robust regulatory mechanisms to ensure that flagellar morphogenesis follows a defined path, with each component self-assembling to predetermined dimensions. The flagellar rod acts as a driveshaft to transmit torque from the cytoplasmic rotor to the external filament. The rod self-assembles to a defined length of ~25 nanometers. Here, we provide evidence that rod length is limited by the width of the periplasmic space between the inner and outer membranes. The length of Braun's lipoprotein determines periplasmic width by tethering the outer membrane to the peptidoglycan layer