An SREBP-Responsive microRNA Operon Contributes to a Regulatory Loop for Intracellular Lipid Homeostasis

SummarySterol regulatory element-binding proteins (SREBPs) have evolved as a focal point for linking lipid synthesis with other pathways that regulate cell growth and survival. Here, we have uncovered a polycistrionic microRNA (miRNA) locus that is activated directly by SREBP-2. Two of the encoded miRNAs, miR-182 and miR-96, negatively regulate the expression of Fbxw7 and Insig-2, respectively, and both are known to negatively affect nuclear SREBP accumulation. Direct manipulation of this miRNA pathway alters nuclear SREBP levels and endogenous lipid synthesis. Thus, we have uncovered a mechanism for the regulation of intracellular lipid metabolism mediated by the concerted action of a pair of miRNAs that are expressed from the same SREBP-2-regulated miRNA locus, and each targets a different protein of the multistep pathway that regulates SREBP function. These studies reveal an miRNA “operon” analogous to the classic model for genetic control in bacterial regulatory systems

On the annual variability of Antarctic aerosol size distributions at Halley Research Station

The Southern Ocean and Antarctic region currently best represent one of the few places left on our planet with conditions similar to the preindustrial age. Currently, climate models have a low ability to simulate conditions forming the aerosol baseline; a major uncertainty comes from the lack of understanding of aerosol size distributions and their dynamics. Contrasting studies stress that primary sea salt aerosol can contribute significantly to the aerosol population, challenging the concept of climate biogenic regulation by new particle formation (NPF) from dimethyl sulfide marine emissions. We present a statistical cluster analysis of the physical characteristics of particle size distributions (PSDs) collected at Halley (Antarctica) for the year 2015 (89 % data coverage; 6-209 nm size range; daily size resolution). By applying the Hartigan-Wong k-mean method we find eight clusters describing the entire aerosol population. Three clusters show pristine average low particle number concentrations (<121-179 cm(-3)) with three main modes (30, 75-95 and 135-160 nm) and represent 57 % of the annual PSD (up to 89 %-100 % during winter and 34 %-65 % during summer based on monthly averages). Nucleation and Aitken mode PSD clusters dominate summer months (SeptemberJanuary, 59 %-90 %), whereas a clear bimodal distribution (43 and 134 nm, respectively; Hoppel minimum at mode 75 nm) is seen only during the December-April period (6%-21 %). Major findings of the current work include: (1) NPF and growth events originate from both the sea ice marginal zone and the Antarctic plateau, strongly suggesting multiple vertical origins, including the marine boundary layer and free troposphere; (2) very low particle number concentrations are detected for a substantial part of the year (57 %), including summer (34 %-65 %), suggesting that the strong annual aerosol concentration cycle is driven by a short temporal interval of strong NPF events; (3) a unique pristine aerosol cluster is seen with a bimodal size distribution (75 and 160 nm, respectively), strongly associated with high wind speed and possibly associated with blowing snow and sea spray sea salt, dominating the winter aerosol population (34 %-54 %). A brief comparison with two other stations (Dome C - Concordia- and King Sejong Station) during the year 2015 (240 d overlap) shows that the dynamics of aerosol number concentrations and distributions are more complex than the simple sulfate-sea-spray binary combination, and it is likely that an array of additional chemical components and processes drive the aerosol population. A conceptual illustration is proposed indicating the various atmospheric processes related to the Antarctic aerosols, with particular emphasis on the origin of new particle formation and growth.Peer reviewe

Meson Exchange Effect on Color Superconductivity

We investigate the effects of pion and gluon exchanges on the formation of two-flavor color superconductivity at moderate density, $\mu <1 GeV$. The chiral quark model proposed by Manohar and Georgi containing pions as well as gluons is employed to show that the pion exchange reduces substantially the value of the superconducting gap gotten with the gluon exchange only. It turns out that the pion exchanges produce a repulsion between quark-quark pair in a spin and isospin singlet state. We suggest that the phase consisiting of pions, gluons and quarks is one of the candidates of in-medium QCD phase at moderate density.Comment: 8 pages, 1 figure, minor correction

Association between Hypertension and Retinal Vascular Features in Ultra-Widefield Fundus Imaging

Objective: Changes to the retinal vasculature are known to be associated with hypertension independently of traditional risk factors. We investigated whether measurements of retinal vascular calibre from ultra-widefield fundus imaging were associated with hypertensive status.Methods: We retrospectively collected and semiautomatically measured ultra-widefield retinal fundus images from a subset of participants enrolled in an ongoing population study of ageing, categorised as normotensive or hypertensive according to thresholds on systolic/diastolic blood pressure (140/90 mm Hg) measured in a clinical setting. Vascular calibre in the peripheral retina was measured to calculate the nasal-annular arteriole:venule ratio (NA-AVR), a novel combined parameter.Results: Left and right eyes were analysed from 440 participants (aged 50-59 years, mean age of 54.6±2.9 years, 247, 56.1% women), including 151 (34.3%) categorised as hypertensive. Arterioles were thinner and the NA-AVR was smaller in people with hypertension. The area under the receiver operating characteristic curve of NA-AVR for hypertensive status was 0.73 (95% CI 0.68 to 0.78) using measurements from left eyes, while for right eyes, it was 0.64 (95% CI 0.59 to 0.70), representing evidence of a statistically significant difference between the eyes (p=0.020).Conclusions: Semiautomated measurements of NA-AVR in ultra-widefield fundus imaging were associated with hypertension. With further development, this may help screen people attending routine eye health check-ups for high blood pressure. These individuals may then follow a care pathway for suspected hypertension. Our results showed differences between left and right eyes, highlighting the importance of investigating both eyes of a patient.</p

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179

The application of polymerized lipid vesicles as colorimetric biosensors for real-time detection of pathogens in drinking water

The inadequate treatments given to the served waste water which are disposal to the rivers and sea coast are the major sources of faecal Microorganisms and enteric bacterial pathogens. They are among the most serious effects of water pollution bringing risks on public health. None of the current methods for detection of pathogens offer real-time on site solutions, are capable of delivering a simple visual detection signal, or can be easily instrumented as an indicator of the presence of a pathogen in water. The use of lipid vesicles incorporating Polydiacetylenes (PDAs) for the development of biosensors for \u201creal-time\u201d detection of pathogens has become an alternative, due to its potential for simple colorimetric response against harmful environmental effectors. However, its actual application in the field has been complicated because lipid vesicles are unable to respond specifically to environmental changes. In this paper, we report several experimental trials leading to improved response in the detection of flagellated pathogens in drinking water. Chromatic biomimetic membranes of TRCDA/DMPC and TRCDA/DMPC/Tryptophan were used in agar and liquid media, which were challenged with different amounts of Escherichia coli and Salmonella typhimurium . In addition, the effect of some divalent cations on the interaction with vesicles TRCDA/DMPC was investigated. The results indicated an improvement in the response times, both visually and quantitatively, through the use of TRIS-EDTA and proper growing conditions for E. coli and Salmonella. With the application of both conditions, it was possible by incubation at 35\ubaC to promote bacterial growth, therefore avoiding a dramatic effect on the colour change over control samples which may invalidate the test. Our experiments indicated that the minimum bacterial concentration necessary to produce the transition from blue to red on the vesicles as biosensor approaches 108 CFU/ml within 4 hrs, faster than traditional methods such as MPN or plate count agar. We present here incubations of samples of contaminated water at 35\ubaC, in agar plates containing chromatic biomimetic membranes of TRCDA/DMPC. A measurable colour transition is obtained within a reaction time of four hrs, which compares favourably with detection times between seven to 24 hrs corresponding to available tests

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Reaction rates and transport in neutron stars

Understanding signals from neutron stars requires knowledge about the transport inside the star. We review the transport properties and the underlying reaction rates of dense hadronic and quark matter in the crust and the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes, references updated, overview graphic added in the introduction, improvements in Sec IV.A.