Motifs from the deep

Because of the increasing recognition of the importance of non-coding RNAs in gene regulation, there is considerable interest in identifying RNA motifs in genomic data. In a recent report in BMC Genomics, Breaker and colleagues describe a new algorithm for identifying functional noncoding RNAs in metagenomic sequences of marine organisms, a strategy that may be particularly effective for discovering new and unique riboswitches

Localization of the Carnation Italian ringspot virus replication protein p36 to the mitochondrial outer membrane is mediated by an internal targeting signal and the TOM complex

<p>Abstract</p> <p>Background</p> <p><it>Carnation Italian ringspot virus </it>(CIRV) is a positive-strand RNA virus that causes massive structural alterations of mitochondria in infected host cells, the most conspicuous being the formation of numerous internal vesicles/spherules that are derived from the mitochondrial outer membrane and serve as the sites for viral RNA replication. While the membrane-bound components of the CIRV replication complex, including a 36-kD RNA-binding protein (p36), are known to be essential for these changes in mitochondrial morphology and are relatively well characterized in terms of their roles in nascent viral RNA synthesis, how these proteins are specifically targeted and inserted into mitochondria is poorly defined.</p> <p>Results</p> <p>Here we report on the molecular signal responsible for sorting p36 to the mitochondrial outer membrane. Using a combination of gain-of-function assays with portions of p36 fused to reporter proteins and domain-swapping assays with p36 and another closely-related viral RNA-binding protein, p33, that sorts specifically to the peroxisomal boundary membrane, we show that the mitochondrial targeting information in p36 resides within its two transmembrane domains (TMDs) and intervening hydrophilic loop sequence. Comprehensive mutational analysis of these regions in p36 revealed that the primary targeting determinants are the moderate hydrophobicity of both TMDs and the positively-charged face of an amphipathic helix within the intervening loop sequence. We show also using bimolecular fluorescence complementation (BiFC) that p36 interacts with certain components of the translocase complex in the mitochondrial outer membrane (TOM), but not with the sorting and assembly machinery (SAM).</p> <p>Conclusion</p> <p>Our results provide insight to how viruses, such as CIRV, exploit specific host-cell protein sorting pathways to facilitate their replication. The characterization of the targeting and insertion of p36 into the mitochondrial outer membrane also sheds light on the mechanisms involved in sorting of host-cell membrane proteins to mitochondria, a process that has been largely unexplored in plants.</p

Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation

Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer’s disease (AD). Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine-rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto-proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies

Gas Emmision Testing of Fuel Based Vehicles at Banda Aceh, Indonesia

A gas emmision decent testing of vehicles based on fuel has been done by EIA (Environmental Impact and Analysis). It is important to do the testing to determine the vehicles meet the technical requirements and road-worthy. The results showed that for 1.572 vehicles which is performing emissions testing have obtained 11% that could be potentially pollute the air on vehicles that using gasoline, and 42% on vehicles that using diesel. Based on the total number of four-wheeled vehicles that performed emissions testing in the city of Banda Aceh showed that 82% environmentally friendly vehicles and 18% potentially pollute the air

Morbidity and mortality in homeless individuals, prisoners, sex workers, and individuals with substance use disorders in high-income countries: a systematic review and meta-analysis.

BACKGROUND: Inclusion health focuses on people in extremely poor health due to poverty, marginalisation, and multimorbidity. We aimed to review morbidity and mortality data on four overlapping populations who experience considerable social exclusion: homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library for studies published between Jan 1, 2005, and Oct 1, 2015. We included only systematic reviews, meta-analyses, interventional studies, and observational studies that had morbidity and mortality outcomes, were published in English, from high-income countries, and were done in populations with a history of homelessness, imprisonment, sex work, or substance use disorder (excluding cannabis and alcohol use). Studies with only perinatal outcomes and studies of individuals with a specific health condition or those recruited from intensive care or high dependency hospital units were excluded. We screened studies using systematic review software and extracted data from published reports. Primary outcomes were measures of morbidity (prevalence or incidence) and mortality (standardised mortality ratios [SMRs] and mortality rates). Summary estimates were calculated using a random effects model. FINDINGS: Our search identified 7946 articles, of which 337 studies were included for analysis. All-cause standardised mortality ratios were significantly increased in 91 (99%) of 92 extracted datapoints and were 11·86 (95% CI 10·42-13·30; I2=94·1%) in female individuals and 7·88 (7·03-8·74; I2=99·1%) in men. Summary SMR estimates for the International Classification of Diseases disease categories with two or more included datapoints were highest for deaths due to injury, poisoning, and other external causes, in both men (7·89; 95% CI 6·40-9·37; I2=98·1%) and women (18·72; 13·73-23·71; I2=91·5%). Disease prevalence was consistently raised across the following categories: infections (eg, highest reported was 90% for hepatitis C, 67 [65%] of 103 individuals for hepatitis B, and 133 [51%] of 263 individuals for latent tuberculosis infection), mental health (eg, highest reported was 9 [4%] of 227 individuals for schizophrenia), cardiovascular conditions (eg, highest reported was 32 [13%] of 247 individuals for coronary heart disease), and respiratory conditions (eg, highest reported was 9 [26%] of 35 individuals for asthma). INTERPRETATION: Our study shows that homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals experience extreme health inequities across a wide range of health conditions, with the relative effect of exclusion being greater in female individuals than male individuals. The high heterogeneity between studies should be explored further using improved data collection in population subgroups. The extreme health inequity identified demands intensive cross-sectoral policy and service action to prevent exclusion and improve health outcomes in individuals who are already marginalised. FUNDING: Wellcome Trust, National Institute for Health Research, NHS England, NHS Research Scotland Scottish Senior Clinical Fellowship, Medical Research Council, Chief Scientist Office, and the Central and North West London NHS Trust

KMT-2016-BLG-1107: A New Hollywood-Planet Close/Wide Degeneracy

We show that microlensing event KMT-2016-BLG-1107 displays a new type of degeneracy between wide-binary and close-binary Hollywood events in which a giant-star source envelops the planetary caustic. The planetary anomaly takes the form of a smooth, two-day "bump" far out on the falling wing of the light curve, which can be interpreted either as the source completely enveloping a minor-image caustic due to a close companion with mass ratio $q=0.036$, or partially enveloping a major-image caustic due to a wide companion with $q=0.004$. The best estimates of the companion masses are both in the planetary regime ($3.3^{+3.5}_{-1.8}\,M_{\rm jup}$ and $0.090^{+0.096}_{-0.037}\,M_{\rm jup}$) but differ by an even larger factor than the mass ratios due to different inferred host masses. We show that the two solutions can be distinguished by high-resolution imaging at first light on next-generation ("30m") telescopes. We provide analytic guidance to understand the conditions under which this new type of degeneracy can appear.Comment: 23 pages, 7 figures, accepted for publication in A

Perturbation evolution in cosmologies with a decaying cosmological constant

Structure formation models with a cosmological constant are successful in explaining large-scale structure data, but are threatened by the magnitude-redshift relation for Type Ia supernovae. This has led to discussion of models where the cosmological `constant' decays with time, which might anyway be better motivated in a particle physics context. The simplest such models are based on scalar fields, and general covariance demands that a time-evolving scalar field also supports spatial perturbations. We consider the effect of such perturbations on the growth of adiabatic energy density perturbations in a cold dark matter component. We study two types of model, one based on an exponential potential for the scalar field and the other on a pseudo-Nambu Goldstone boson. For each potential, we study two different scenarios, one where the scalar field presently behaves as a decaying cosmological constant and one where it behaves as dust. The initial scalar field perturbations are fixed by the adiabatic condition, as expected from the inflationary cosmology, though in fact we show that the choice of initial condition is of little importance. Calculations are carried out in both the zero-shear (conformal newtonian) and uniform-curvature gauges. We find that both potentials allow models which can provide a successful alternative to cosmological constant models.Comment: 14 pages RevTeX file with three figures incorporated (uses RevTeX and epsf). Also available by e-mailing ARL, or by WWW at http://star-www.maps.susx.ac.uk/papers/lsstru_papers.html Revised version corrects an error in Eq10; results unchange