Showing papers by "University of Nice Sophia Antipolis published in 2012"

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes.

Abstract: The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of “brown adipocytes” within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional “brown-like” adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK–dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C–/– mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote “browning” of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology.

Energy Consumption, Economic Growth and CO2 Emissions in Middle East and North African Countries

Abstract: This article extends the recent findings of Liu (2005), Ang (2007), Apergis et al. (2009) and Payne (2010) by implementing recent bootstrap panel unit root tests and cointegration techniques to investigate the relationship between carbon dioxide emissions, energy consumption, and real GDP for 12 Middle East and North African Countries (MENA) over the period 1981–2005. Our results show that in the long-run energy consumption has a positive significant impact on CO2 emissions. More interestingly, we show that real GDP exhibits a quadratic relationship with CO2 emissions for the region as a whole. However, although the estimated long-run coefficients of income and its square satisfy the EKC hypothesis in most studied countries, the turning points are very low in some cases and very high in other cases, hence providing poor evidence in support of the EKC hypothesis. Thus, our findings suggest that not all MENA countries need to sacrifice economic growth to decrease their emission levels as they may achieve CO2 emissions reduction via energy conservation without negative long-run effects on economic growth.

Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing.

Abstract: Little is known about how organ growth is monitored and coordinated with the developmental timing in complex organisms. In insects, impairment of larval tissue growth delays growth and morphogenesis, revealing a coupling mechanism. We carried out a genetic screen in Drosophila to identify molecules expressed by growing tissues participating in this coupling and identified dilp8 as a gene whose silencing rescues the developmental delay induced by abnormally growing tissues. dilp8 is highly induced in conditions where growth impairment produces a developmental delay. dilp8 encodes a peptide for which expression and secretion are sufficient to delay metamorphosis without affecting tissue integrity. We propose that Dilp8 peptide is a secreted signal that coordinates the growth status of tissues with developmental timing.

Discovery of Small-Scale Spiral Structures in the Disk of SAO 206462 (HD 135344B): Implications for the Physical State of the Disk from Spiral Density Wave Theory

Abstract: We present high-resolution, H-band, imaging observations, collected with Subaru/HiCIAO, of the scattered light from the transitional disk around SAO 206462 (HD 135344B). Although previous sub-mm imagery suggested the existence of the dust-depleted cavity at r approximates 46 AU, our observations reveal the presence of scattered light components as close as 0".2 (approx 28 AU) from the star. Moreover, we have discovered two small-scale spiral structures lying within 0".5 (approx 70 AU). We present models for the spiral structures using the spiral density wave theory, and derive a disk aspect ratio of h approx 0.1, which is consistent with previous sub-mm observations. This model can potentially give estimates of the temperature and rotation profiles of the disk based on dynamical processes, independently from sub-mm observations. It also predicts the evolution of the spiral structures, which can be observable on timescales of 10-20 years, providing conclusive tests of the model. While we cannot uniquely identify the origin of these spirals, planets embedded in the disk may be capable of exciting the observed morphology. Assuming that this is the case, we can make predictions on the locations and, possibly, the masses of the unseen planets. Such planets may be detected by future multi-wavelengths observations.

Scientific objectives of Einstein Telescope

Abstract: The advanced interferometer network will herald a new era in observational astronomy. There is a very strong science case to go beyond the advanced detector network and build detectors that operate in a frequency range from 1 Hz to 10 kHz, with sensitivity a factor 10 better in amplitude. Such detectors will be able to probe a range of topics in nuclear physics, astronomy, cosmology and fundamental physics, providing insights into many unsolved problems in these areas.

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and interactions with Plasmodium falciparum infection

Abstract: The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.

Oral complications of cancer and cancer therapy: from cancer treatment to survivorship.

Abstract: Answer questions and earn CME/CNE Oral complications resulting from cancer and cancer therapies cause acute and late toxicities that may be underreported, underrecognized, and undertreated. Recent advances in cancer treatment have led to changes in the incidence, nature, and severity of oral complications. As the number of survivors increases, it is becoming increasingly recognized that the aggressive management of oral toxicities is needed to ensure optimal long-term oral health and general well-being. Advances in care have had an impact on previously recognized oral complications and are leading to newly recognized adverse effects. Here, the authors briefly review advances in cancer therapy, including recent advances in surgery, oral care, radiation therapy, hematopoietic cell transplantation, and medical oncology; describe how these advances affect oral health; and discuss the frequent and/or severe oral health complications associated with cancer and cancer treatment and their effect upon long-term health. Although some of the acute oral toxicities of cancer therapies may be reduced, they remain essentially unavoidable. The significant impact of long-term complications requires increased awareness and recognition to promote prevention and appropriate intervention. It is therefore important for the primary oncologist to be aware of these complications so that appropriate measures can be implemented in a timely manner. Prevention and management is best provided via multidisciplinary health care teams, which must be integrated and communicate effectively in order to provide the best patient care in a coordinated manner at the appropriate time.

Cancer metabolism: current perspectives and future directions.

Abstract: Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells.

Statistical Study of the Early Solar System's Instability with Four, Five, and Six Giant Planets

Abstract: Several properties of the solar system, including the wide radial spacing and orbital eccentricities of giant planets, can be explained if the early solar system evolved through a dynamical instability followed by migration of planets in the planetesimal disk. Here we report the results of a statistical study, in which we performed nearly 104 numerical simulations of planetary instability starting from hundreds of different initial conditions. We found that the dynamical evolution is typically too violent, if Jupiter and Saturn start in the 3:2 resonance, leading to ejection of at least one ice giant from the solar system. Planet ejection can be avoided if the mass of the transplanetary disk of planetesimals was large (M disk 50 M Earth), but we found that a massive disk would lead to excessive dynamical damping (e.g., final e 55 0.01 compared to present e 55 = 0.044, where e 55 is the amplitude of the fifth eccentric mode in the Jupiter's orbit), and to smooth migration that violates constraints from the survival of the terrestrial planets. Better results were obtained when the solar system was assumed to have five giant planets initially, and one ice giant, with mass comparable to that of Uranus and Neptune, was ejected into interstellar space by Jupiter. The best results were obtained when the ejected planet was placed into the external 3:2 or 4:3 resonance with Saturn and M disk 20 M Earth. The range of possible outcomes is rather broad in this case, indicating that the present solar system is neither a typical nor expected result for a given initial state, and occurs, in best cases, with only a 5% probability (as defined by the success criteria described in the main text). The case with six giant planets shows interesting dynamics but does offer significant advantages relative to the five-planet case.

An Archaean heavy bombardment from a destabilized extension of the asteroid belt

Abstract: The Late Heavy Bombardment lasted much longer than previously thought, up to 1.7 billion years ago on Earth, with impacts on the Moon and Earth coming mostly from the E-belt-survivor Hungaria asteroids. The Late Heavy Bombardment was a period of time, generally put at about 4.1 billion to 3.8 billion years ago, when the inner planets of the Solar System were subjected to a high-frequency barrage of asteroids. This left its mark on the Moon, but on Earth the craters quickly disappeared owing to tectonic processes and erosion. In the first of two papers on the bombardment, Brandon Johnson and Jay Melosh determine the properties of the asteroids by looking at spherule beds: layers of debris ejected during the impacts. The thickness of spherule layers is expected to vary according to the size of the impactor and the speed at which it hit Earth. This historical record of impacts indicates that the number of projectiles colliding with Earth was substantially higher 3.5 billion years ago than it is today, with a gradual decline in the number of strikes after the Late Heavy Bombardment. Bottke et al. modelled the evolution of an asteroid belt that extended farther towards Mars than the present one. They find that most of the impactors traced by the spherule beds probably originated in this 'E-belt', which was disrupted during migrations of some of the giant planets. The barrage of comets and asteroids that produced many young lunar basins (craters over 300 kilometres in diameter) has frequently been called the Late Heavy Bombardment1 (LHB). Many assume the LHB ended about 3.7 to 3.8 billion years (Gyr) ago with the formation of Orientale basin2,3. Evidence for LHB-sized blasts on Earth, however, extend into the Archaean and early Proterozoic eons, in the form of impact spherule beds: globally distributed ejecta layers created by Chicxulub-sized or larger cratering events4. At least seven spherule beds have been found that formed between 3.23 and 3.47 Gyr ago, four between 2.49 and 2.63 Gyr ago, and one between 1.7 and 2.1 Gyr ago5,6,7,8,9. Here we report that the LHB lasted much longer than previously thought, with most late impactors coming from the E belt, an extended and now largely extinct portion of the asteroid belt between 1.7 and 2.1 astronomical units from Earth. This region was destabilized by late giant planet migration10,11,12,13. E-belt survivors now make up the high-inclination Hungaria asteroids14,15. Scaling from the observed Hungaria asteroids, we find that E-belt projectiles made about ten lunar basins between 3.7 and 4.1 Gyr ago. They also produced about 15 terrestrial basins between 2.5 and 3.7 Gyr ago, as well as around 70 and four Chicxulub-sized or larger craters on the Earth and Moon, respectively, between 1.7 and 3.7 Gyr ago. These rates reproduce impact spherule bed and lunar crater constraints.

Design of computer experiments: space filling and beyond

Abstract: When setting up a computer experiment, it has become a standard practice to select the inputs spread out uniformly across the available space. These so-called space-filling designs are now ubiquitous in corresponding publications and conferences. The statistical folklore is that such designs have superior properties when it comes to prediction and estimation of emulator functions. In this paper we want to review the circumstances under which this superiority holds, provide some new arguments and clarify the motives to go beyond space-filling. An overview over the state of the art of space-filling is introducing and complementing these results.

The Structure of Mediterranean Rocky Reef Ecosystems across Environmental and Human Gradients, and Conservation Implications

Abstract: Historical exploitation of the Mediterranean Sea and the absence of rigorous baselines makes it difficult to evaluate the current health of the marine ecosystems and the efficacy of conservation actions at the ecosystem level. Here we establish the first current baseline and gradient of ecosystem structure of nearshore rocky reefs at the Mediterranean scale. We conducted underwater surveys in 14 marine protected areas and 18 open access sites across the Mediterranean, and across a 31-fold range of fish biomass (from 3.8 to 118 g m 22 ). Our data showed remarkable variation in the structure of rocky reef ecosystems. Multivariate analysis showed three alternative community states: (1) large fish biomass and reefs dominated by non-canopy algae, (2) lower fish biomass but abundant native algal canopies and suspension feeders, and (3) low fish biomass and extensive barrens, with areas covered by turf algae. Our results suggest that the healthiest shallow rocky reef ecosystems in the Mediterranean have both large fish and algal biomass. Protection level and primary production were the only variables significantly correlated to community biomass structure. Fish biomass was significantly larger in well-enforced no-take marine reserves, but there were no significant differences between multi-use marine protected areas (which allow some fishing) and open access areas at the regional scale. The gradients reported here represent a trajectory of degradation that can be used to assess the health of any similar habitat in the Mediterranean, and to evaluate the efficacy of marine protected areas.

Black mamba venom peptides target acid-sensing ion channels to abolish pain

Abstract: Polypeptide toxins have played a central part in understanding physiological and physiopathological functions of ion channels. In the field of pain, they led to important advances in basic research and even to clinical applications. Acid-sensing ion channels (ASICs) are generally considered principal players in the pain pathway, including in humans. A snake toxin activating peripheral ASICs in nociceptive neurons has been recently shown to evoke pain. Here we show that a new class of three-finger peptides from another snake, the black mamba, is able to abolish pain through inhibition of ASICs expressed either in central or peripheral neurons. These peptides, which we call mambalgins, are not toxic in mice but show a potent analgesic effect upon central and peripheral injection that can be as strong as morphine. This effect is, however, resistant to naloxone, and mambalgins cause much less tolerance than morphine and no respiratory distress. Pharmacological inhibition by mambalgins combined with the use of knockdown and knockout animals indicates that blockade of heteromeric channels made of ASIC1a and ASIC2a subunits in central neurons and of ASIC1b-containing channels in nociceptors is involved in the analgesic effect of mambalgins. These findings identify new potential therapeutic targets for pain and introduce natural peptides that block them to produce a potent analgesia.

Landing a VTOL Unmanned Aerial Vehicle on a Moving Platform Using Optical Flow

Abstract: This paper presents a nonlinear controller for a vertical take-off and landing (VTOL) unmanned aerial vehicle (UAV) that exploits a measurement optical flow to enable hover and landing control on a moving platform, such as, for example, the deck of a sea-going vessel. The VTOL vehicle is assumed to be equipped with a minimum sensor suite [i.e., a camera and an inertial measurement unit (IMU)], manoeuvring over a textured flat target plane. Two different tasks are considered in this paper. The first concerns the stabilization of the vehicle relative to the moving platform that maintains a constant offset from a moving reference. The second concerns regulation of automatic vertical landing onto a moving platform. Rigorous analysis of system stability is provided, and simulations are presented. Experimental results are provided for a quadrotor UAV to demonstrate the performance of the proposed control strategy.

Virgo: a laser interferometer to detect gravitational waves

Abstract: This paper presents a complete description of Virgo, the French-Italian gravitational wave detector. The detector, built at Cascina, near Pisa (Italy), is a very large Michelson interferometer, with 3 km-long arms. In this paper, following a presentation of the physics requirements, leading to the specifications for the construction of the detector, a detailed description of all its different elements is given. These include civil engineering infrastructures, a huge ultra-high vacuum (UHV) chamber (about 6000 cubic metres), all of the optical components, including high quality mirrors and their seismic isolating suspensions, all of the electronics required to control the interferometer and for signal detection. The expected performances of these different elements are given, leading to an overall sensitivity curve as a function of the incoming gravitational wave frequency. This description represents the detector as built and used in the first data-taking runs. Improvements in different parts have been and continue to be performed, leading to better sensitivities. These will be detailed in a forthcoming paper.

Identification of Adipose Tissue Dendritic Cells Correlated With Obesity-Associated Insulin-Resistance and Inducing Th17 Responses in Mice and Patients

Abstract: T-cell regulation in adipose tissue provides a link between inflammation and insulin resistance. Because of alterations in adipose tissue T-cell composition in obesity, we aimed to identify the antigen-presenting cells in adipose tissue of obese mice and patients with insulin resistance. Dendritic cells (DCs) and T cells were studied in mice and in two cohorts of obese patients. In lean mice, only CD11c(+) DCs were detected in adipose tissue. Adoptive transfer of naive CD4(+) T cells in Rag1(-/-) mice led to a predominant Th1 response in adipose tissue. In contrast, during obesity DCs (human CD11c(+)CD1c(+) and mouse CD11c(high)F4/80(low)) accumulated in adipose tissue. CD11c(high)F4/80(low) DCs from obese mice induced Th17 differentiation. In patients, the presence of CD11c(+)CD1c(+) DCs correlated with the BMI and with an elevation in Th17 cells. In addition, these DCs led to ex vivo Th17 differentiation. CD1c gene expression further correlated with homeostatic model assessment-insulin resistance in the subcutaneous adipose tissue of obese patients. We show for the first time the presence and accumulation of specific DCs in adipose tissue in mouse and human obesity. These DCs were functional and could be important regulators of adipose tissue inflammation by regulating the switch toward Th17 cell responses in obesity-associated insulin resistance.

Circadian rhythms govern cardiac repolarization and arrhythmogenesis

Abstract: Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnormalities in the duration (for example, short or long QT syndromes and heart failure) or pattern (for example, Brugada's syndrome) of myocardial repolarization. Here we provide molecular evidence that links circadian rhythms to vulnerability in ventricular arrhythmias in mice. Specifically, we show that cardiac ion-channel expression and QT-interval duration (an index of myocardial repolarization) exhibit endogenous circadian rhythmicity under the control of a clock-dependent oscillator, kruppel-like factor 15 (Klf15). Klf15 transcriptionally controls rhythmic expression of Kv channel-interacting protein 2 (KChIP2), a critical subunit required for generating the transient outward potassium current. Deficiency or excess of Klf15 causes loss of rhythmic QT variation, abnormal repolarization and enhanced susceptibility to ventricular arrhythmias. These findings identify circadian transcription of ion channels as a mechanism for cardiac arrhythmogenesis.

Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial.

Abstract: Summary Background Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. Methods In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510. Findings Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio [HR] 0·84, 95% CI 0·60–1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69–1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77–1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups. Interpretation Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. Funding Ipsen.

KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron

Abstract: Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins that recruit substrates for Cullin3-based ubiquitin ligase complexes. KLHL3 is coexpressed with NCC and downregulates NCC expression at the cell surface. Our study establishes a role for KLHL3 as a new member of the complex signaling pathway regulating ion homeostasis in the distal nephron and indirectly blood pressure.

Significant and persistent impact of timber harvesting on soil microbial communities in Northern coniferous forests

Abstract: Forest ecosystems have integral roles in climate stability, biodiversity and economic development. Soil stewardship is essential for sustainable forest management. Organic matter (OM) removal and soil compaction are key disturbances associated with forest harvesting, but their impacts on forest ecosystems are not well understood. Because microbiological processes regulate soil ecology and biogeochemistry, microbial community structure might serve as indicator of forest ecosystem status, revealing changes in nutrient and energy flow patterns before they have irreversible effects on long-term soil productivity. We applied massively parallel pyrosequencing of over 4.6 million ribosomal marker sequences to assess the impact of OM removal and soil compaction on bacterial and fungal communities in a field experiment replicated at six forest sites in British Columbia, Canada. More than a decade after harvesting, diversity and structure of soil bacterial and fungal communities remained significantly altered by harvesting disturbances, with individual taxonomic groups responding differentially to varied levels of the disturbances. Plant symbionts, like ectomycorrhizal fungi, and saprobic taxa, such as ascomycetes and actinomycetes, were among the most sensitive to harvesting disturbances. Given their significant ecological roles in forest development, the fate of these taxa might be critical for sustainability of forest ecosystems. Although abundant bacterial populations were ubiquitous, abundant fungal populations often revealed a patchy distribution, consistent with their higher sensitivity to the examined soil disturbances. These results establish a comprehensive inventory of bacterial and fungal community composition in northern coniferous forests and demonstrate the long-term response of their structure to key disturbances associated with forest harvesting.

Dictionary adaptation for online prediction of time series data with kernels

Abstract: During the last few years, kernel methods have been very useful to solve nonlinear identification problems. The main drawback of these methods resides in the fact that the number of elements of the kernel development, i.e., the size of the dictionary, increases with the number of input data, making the solution not suitable for online problems especially time series applications. Recently, Richard, Bermudez and Honeine investigated a method where the size of the dictionary is controlled by a coherence criterion. In this paper, we extend this method by adjusting the dictionary elements in order to reduce the residual error and/or the average size of the dictionary. The proposed method is implemented for time series prediction using the kernel-based affine projection algorithm.

On the genesis and evolution of Integrated Quantum Optics

Abstract: Applications of Integrated Optics to quantum sources, detectors, interfaces, memories and linear optical quantum computing are described in this review. By their inherent compactness, efficiencies, and interconnectability, many of the demonstrated individual devices can clearly serve as building blocks for more complex quantum systems, that could also profit from the incorporation of other guided wave technologies.

Surprisingly diverged populations of Saccharomyces cerevisiae in natural environments remote from human activity.

Abstract: The budding yeast, Saccharomyces cerevisiae, is a leading system in genetics, genomics and molecular biology and is becoming a powerful tool to illuminate ecological and evolutionary principles. However, little is known of the ecology and population structure of this species in nature. Here, we present a field survey of this yeast at an unprecedented scale and have performed population genetics analysis of Chinese wild isolates with different ecological and geographical origins. We also included a set of worldwide isolates that represent the maximum genetic variation of S. cerevisiae documented so far. We clearly show that S. cerevisiae is a ubiquitous species in nature, occurring in highly diversified substrates from human-associated environments as well as habitats remote from human activity. Chinese isolates of S. cerevisiae exhibited strong population structure with nearly double the combined genetic variation of isolates from the rest of the world. We identified eight new distinct wild lineages (CHN I-VIII) from a set of 99 characterized Chinese isolates. Isolates from primeval forests occur in ancient and significantly diverged basal lineages, while those from human-associated environments generally cluster in less differentiated domestic or mosaic groups. Basal lineages from primeval forests are usually inbred, exhibit lineage-specific karyotypes and are partially reproductively isolated. Our results suggest that greatly diverged populations of wild S. cerevisiae exist independently of and predate domesticated isolates. We find that China harbours a reservoir of natural genetic variation of S. cerevisiae and perhaps gives an indication of the origin of the species.

Search for gravitational waves from low mass compact binary coalescence in LIGO's sixth science run and Virgo's science runs 2 and 3

Abstract: We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25M(circle dot); this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90% confidence rate upper limits of the binary coalescence of binary neutron star, neutron star-black hole, and binary black hole systems are 1.3 x 10(-4), 3.1 x 10(-5), and 6.4 x 10(-6) Mpc(-3) yr(-1), respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.