Cellular mRNAs access second ORFs using a novel amino acid sequence-dependent coupled translation termination-reinitiation mechanism

Polycistronic transcripts are considered rare in the human genome. Initiation of translation of internal ORFs of eukaryotic genes has been shown to use either leaky scanning or highly structured IRES regions to access initiation codons. Studies on mammalian viruses identified a mechanism of coupled translation termination-reinitiation that allows translation of an additional ORF. Here, the ribosome terminating translation of ORF-1 translocates upstream to reinitiate translation of ORF-2. We have devised an algorithm to identify mRNAs in the human transcriptome in which the major ORF-1 overlaps a second ORF capable of encoding a product of at least 50 aa in length. This identified 4368 transcripts representing 2214 genes. We investigated 24 transcripts, 22 of which were shown to express a protein from ORF-2 highlighting that 3' UTRs contain protein-coding potential more frequently than previously suspected. Five transcripts accessed ORF-2 using a process of coupled translation termination-reinitiation. Analysis of one transcript, encoding the CASQ2 protein, showed that the mechanism by which the coupling process of the cellular mRNAs was achieved was novel. This process was not directed by the mRNA sequence but required an aspartate-rich repeat region at the carboxyl terminus of the terminating ORF-1 protein. Introduction of wobble mutations for the aspartate codon had no effect, whereas replacing aspartate for glutamate repeats eliminated translational coupling. This is the first description of a coordinated expression of two proteins from cellular mRNAs using a coupled translation termination-reinitiation process and is the first example of such a process being determined at the amino acid level

Geomorphological control on boulder transport and coastal erosion before, during and after an extreme extra-tropical cyclone

Extreme wave events in coastal zones are principal drivers of geomorphic change. Evidence of boulder entrainment and erosional impact during storms is increasing. However, there is currently poor time coupling between pre- and post-storm measurements of coastal boulder deposits. Importantly there are no data reporting shore platform erosion, boulder entrainment and/or boulder transport during storm events – rock coast dynamics during storm events are currently unexplored. Here, we use high-resolution (daily) field data to measure and characterise coastal boulder transport before, during and after the extreme Northeast Atlantic extra-tropical cyclone Johanna in March 2008. Forty-eight limestone fine-medium boulders (n = 46) and coarse cobbles (n = 2) were tracked daily over a 0.1 km2 intertidal area during this multi-day storm. Boulders were repeatedly entrained, transported and deposited, and in some cases broken down (n = 1) or quarried (n = 3), during the most intense days of the storm. Eighty-one percent (n = 39) of boulders were located at both the start and end of the storm. Of these, 92% were entrained where entrainment patterns were closely aligned to wave parameters. These data firmly demonstrate rock coasts are dynamic and vulnerable under storm conditions. No statistically significant relationship was found between boulder size (mass) and net transport distance. Graphical analyses suggest that boulder size limits the maximum longshore transport distance but that for the majority of boulders lying under this threshold, other factors influence transport distance. Paired analysis of 20 similar sized and shaped boulders in different morphogenic zones demonstrates that geomorphological control affects entrainment and transport distance – where net transport distances were up to 39 times less where geomorphological control was greatest. These results have important implications for understanding and for accurately measuring and modelling boulde

Self Calibration of Tomographic Weak Lensing for the Physics of Baryons to Constrain Dark Energy

Numerical studies indicate that uncertainties in the treatment of baryonic physics can affect predictions for shear power spectra at a level that is significant for forthcoming surveys such as DES, SNAP, and LSST. Correspondingly, we show that baryonic effects can significantly bias dark energy parameter measurements. Eliminating such biases by neglecting information in multipoles beyond several hundred leads to weaker parameter constraints by a factor of approximately 2 to 3 compared with using information out to multipoles of several thousand. Fortunately, the same numerical studies that explore the influence of baryons indicate that they primarily affect power spectra by altering halo structure through the relation between halo mass and mean effective halo concentration. We explore the ability of future weak lensing surveys to constrain both the internal structures of halos and the properties of the dark energy simultaneously as a first step toward self calibrating for the physics of baryons. This greatly reduces parameter biases and no parameter constraint is degraded by more than 40% in the case of LSST or 30% in the cases of SNAP or DES. Modest prior knowledge of the halo concentration relation greatly improves even these forecasts. Additionally, we find that these surveys can constrain effective halo concentrations near m~10^14 Msun/h and z~0.2 to better than 10% with shear power spectra alone. These results suggest that inferring dark energy parameters with measurements of shear power spectra can be made robust to baryonic effects and may simultaneously be competitive with other methods to inform models of galaxy formation. (Abridged)Comment: 18 pages, 11 figures. Minor changes reflecting referee's comments. Results and conclusions unchanged. Accepted for publication in Physical Review

LoCoH: nonparameteric kernel methods for constructing home ranges and utilization distributions.

Parametric kernel methods currently dominate the literature regarding the construction of animal home ranges (HRs) and utilization distributions (UDs). These methods frequently fail to capture the kinds of hard boundaries common to many natural systems. Recently a local convex hull (LoCoH) nonparametric kernel method, which generalizes the minimum convex polygon (MCP) method, was shown to be more appropriate than parametric kernel methods for constructing HRs and UDs, because of its ability to identify hard boundaries (e.g., rivers, cliff edges) and convergence to the true distribution as sample size increases. Here we extend the LoCoH in two ways: "fixed sphere-of-influence," or r-LoCoH (kernels constructed from all points within a fixed radius r of each reference point), and an "adaptive sphere-of-influence," or a-LoCoH (kernels constructed from all points within a radius a such that the distances of all points within the radius to the reference point sum to a value less than or equal to a), and compare them to the original "fixed-number-of-points," or k-LoCoH (all kernels constructed from k-1 nearest neighbors of root points). We also compare these nonparametric LoCoH to parametric kernel methods using manufactured data and data collected from GPS collars on African buffalo in the Kruger National Park, South Africa. Our results demonstrate that LoCoH methods are superior to parametric kernel methods in estimating areas used by animals, excluding unused areas (holes) and, generally, in constructing UDs and HRs arising from the movement of animals influenced by hard boundaries and irregular structures (e.g., rocky outcrops). We also demonstrate that a-LoCoH is generally superior to k- and r-LoCoH (with software for all three methods available at http://locoh.cnr.berkeley.edu)

Wavenumber Selection of Convection Rolls in a Box

The dynamics of two‐dimensional Rayleigh–Bénard convection rolls are studied in a finite layer with no‐slip, fixed temperature upper and lower boundaries and no‐slip insulating side walls. The dominant mechanism controlling the number of rolls seen in the layer is an instability concentrated near the side walls. This mechanism significantly narrows the band of stable wavenumbers although it can take a time comparable to the long (horizontal) diffusion time scale to operate

Quantum simulation of multiple-exciton generation in a nanocrystal by a single photon

We have shown theoretically that efficient multiple exciton generation (MEG) by a single photon can be observed in small nanocrystals (NCs). Our quantum simulations that include hundreds of thousands of exciton and multi-exciton states demonstrate that the complex time-dependent dynamics of these states in a closed electronic system yields a saturated MEG effect on a picosecond timescale. Including phonon relaxation confirms that efficient MEG requires the exciton--biexciton coupling time to be faster than exciton relaxation time

A Nova Web Application for Population Viability and Sustainable Harvesting Analyses

Population viability analyses are used to assess the probability that a particular population of individuals will persist as a self-reproducing, ecologically viable entity for a specified period of time. Such models are typically cast as Markov processes that may inter alia include demographic structure (e.g. age, stage, sex), ecological processes through the incorporation of density-dependent reproduction or survival functions, viability thresholds that trigger remedial interventions when breached (e.g. removal of individuals to protect environments), metapopulation structure, stocking, harvesting or translocations of the population. These models can also be used to assess the impacts of harvesting strategies when they include population removal options. Here we present a general Nova modeling framework that integrates all of the above features and generates distributions of outcomes through repeated simulations. The framework incorporates the most relevant ecosystem structures, including metapopulation structure with associated connectivity and movement parameters, age/stage class structure with population-specific life history data, demographic and environmental stochasticity components, and management interventions including off-take, translocation, and stocking components. The NOVA PVA model is available as a responsively configured web application that can be run locally in a browser or on high performance computing systems controlled by a browser-based dashboard. In this talk the structure of the model will be discussed and the operation of the web application will be demonstrated

Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers

BACKGROUND: Highway maintenance workers are constantly and simultaneously exposed to traffic-related particle and noise emissions, and both have been linked to increased cardiovascular morbidity and mortality in population-based epidemiology studies. OBJECTIVES: We aimed to investigate short-term health effects related to particle and noise exposure. METHODS: We monitored 18 maintenance workers, during as many as five 24-hour periods from a total of 50 observation days. We measured their exposure to fine particulate matter (PM2.5), ultrafine particles, noise, and the cardiopulmonary health endpoints: blood pressure, pro-inflammatory and pro-thrombotic markers in the blood, lung function and fractional exhaled nitric oxide (FeNO) measured approximately 15 hours post-work. Heart rate variability was assessed during a sleep period approximately 10 hours post-work. RESULTS: PM2.5 exposure was significantly associated with C-reactive protein and serum amyloid A, and negatively associated with tumor necrosis factor α. None of the particle metrics were significantly associated with von Willebrand factor or tissue factor expression. PM2.5 and work noise were associated with markers of increased heart rate variability, and with increased HF and LF power. Systolic and diastolic blood pressure on the following morning were significantly associated with noise exposure after work, and non-significantly associated with PM2.5. We observed no significant associations between any of the exposures and lung function or FeNO. CONCLUSIONS: Our findings suggest that exposure to particles and noise during highway maintenance work might pose a cardiovascular health risk. Actions to reduce these exposures could lead to better health for this population of workers

Troisier sign and Virchow node: the anatomy and pathology of pulmonary adenocarcinoma metastasis to a supraclavicular lymph node

Metastatic spread of cancer via the thoracic duct may lead to an enlargement of the left supraclavicular node, known as the Virchow node (VN), leading to an appreciable mass that can be recognized clinically — a Troisier sign. The VN is of profound clinical importance; however, there have been few studies of its regional anatomical relationships. Our report presents a case of a Troisier sign/VN discovered during cadaveric dissection in an individual whose cause of death was, reportedly, chronic obstructive pulmonary disease. The VN was found to arise from an antecedent pulmonary adenocarcinoma. Our report includes a regional study of the anatomy as well as relevant gross pathology and histopathology. Our anatomical findings suggest that the VN may contribute to vascular thoracic outlet syndrome as well as the brachial plexopathy of neurogenic thoracic outlet syndrome. Further, the VN has the potential to cause compression of the phrenic nerve, contributing to unilateral phrenic neuropathy and subsequent dyspnea. Recognition of the Troisier sign/VN is of great clinical importance. Similarly, an appreciation of the anatomy surrounding the VN, and the potential for the enlarged node to encroach on neurovascular structures, is also important in the study of a patient. The presence of a Troisier sign/VN should be assessed when thoracic outlet syndrome and phrenic neuropathy are suspected. Conversely, when a VN is identified, the possibility of concomitant or subsequent thoracic outlet syndrome and phrenic neuropathy should be considered