Steatogenesis in adult-onset type II citrullinemia is associated with down-regulation of PPARα

AbstractSLC25A13 (citrin or aspartate–glutamate carrier 2) is located in the mitochondrial membrane in the liver and its genetic deficiency causes adult-onset type II citrullinemia (CTLN2). CTLN2 is one of the urea cycle disorders characterized by sudden-onset hyperammonemia due to reduced argininosuccinate synthase activity. This disorder is frequently accompanied with hepatosteatosis in the absence of obesity and ethanol consumption. However, the precise mechanism of steatogenesis remains unclear. The expression of genes associated with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from 16 CTLN2 patients and compared with 7 healthy individuals. Although expression of hepatic genes associated with lipogenesis and TG hydrolysis was not changed, the mRNAs encoding enzymes/proteins involved in FA oxidation (carnitine palmitoyl-CoA transferase 1α, medium- and very-long-chain acyl-CoA dehydrogenases, and acyl-CoA oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1), were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial β-oxidation activity. Consistent with these findings, the expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of hepatic lipid metabolism, was significantly down-regulated. Hepatic PPARα expression was inversely correlated with severity of steatosis and circulating ammonia and citrulline levels. Additionally, phosphorylation of c-Jun-N-terminal kinase was enhanced in CTLN2 livers, which was likely associated with lower hepatic PPARα. Collectively, down-regulation of PPARα is associated with steatogenesis in CTLN2 patients. These findings provide a novel link between urea cycle disorder, lipid metabolism, and PPARα

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction

Background: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cardiac troponin (cTn) assays. However, it remains to be determined how to diagnose, risk stratify and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. Methods: Patients presenting to the Emergency Department with chest pain, enrolled in the CHOPIN study, were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic (ROC) curve analysis. The biomarkers analyzed were cTnI, copeptin, mid-regional pro-atrial natriuretic peptide (MRproANP), C-terminal pro-endothelin-1 (CT-proET1), mid-regional pro-adrenomedullin (MRproADM) and procalcitonin. Prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (MACE: a composite of acute MI, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. Results: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, while those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the ROC curve (AUC) for the diagnosis of T2MI was higher for CT-proET1, MRproADM and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, p = 0.294). Addition of biomarkers to the clinical model yielded the highest AUC (0.917). Other biomarkers, but not cTnI, were associated with mortality and MACE at 180-day among all patients, with no interaction between the diagnosis of T1MI or T2MI. Conclusions: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. Additionally, all biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of type of MI

Sonochemically Fabricated Microelectrode Arrays for Use as Sensing Platforms

The development, manufacture, modification and subsequent utilisation of sonochemically-formed microelectrode arrays is described for a range of applications. Initial fabrication of the sensing platform utilises ultrasonic ablation of electrochemically insulating polymers deposited upon conductive carbon substrates, forming an array of up to 70,000 microelectrode pores cm−2. Electrochemical and optical analyses using these arrays, their enhanced signal response and stir-independence area are all discussed. The growth of conducting polymeric “mushroom” protrusion arrays with entrapped biological entities, thereby forming biosensors is detailed. The simplicity and inexpensiveness of this approach, lending itself ideally to mass fabrication coupled with unrivalled sensitivity and stir independence makes commercial viability of this process a reality. Application of microelectrode arrays as functional components within sensors include devices for detection of chlorine, glucose, ethanol and pesticides. Immunosensors based on microelectrode arrays are described within this monograph for antigens associated with prostate cancer and transient ischemic attacks (strokes)

On the application of scattering matrix measurements to detection and identification of major types of airborne aerosol particles: Volcanic ash, desert dust and pollen

This work has been funded by the excellence research program of the Andalusian Regional Government, grant number P18RT-1854, the National Plan of Scientific and Technical Research and Innovation of the Spanish Ministry of Science and Innovation, grant number RTI2018-095330-B-100 (LEONIDAS), and the "Center of Excellence Severo Ochoa" award to the Instituto de Astrofisica de Andalucia (SEV-2017-0709) by the Spanish State Agency for Research. J.C.G.M acknowledges financial support from the Ramon y Cajal Program of the Spanish Ministry of Science and Innovation (RYC-2016-19570). JoseLuis de la Rosa, JoseAntonio Ruiz and Shi Zongbo are acknowledged for collecting the Sahara-OSN and GobiBeijing desert dust samples.Atmospheric aerosols play key roles in climate and have important impacts on human activities and health. Hence, much effort is directed towards developing methods of improved detection and discrimina- tion of different types of aerosols. Among these, light scattering-based detection of aerosol offers several advantages including applications in both in situ and remote sensing devices. In this work, new scat- tering matrix measurements for two samples of airborne desert dust collected in Spain and China are reported. The average extrapolated scattering matrices of airborne desert dust and of volcanic ash at two wavelengths have been calculated and compared with the aim of finding criteria to distinguish these two types of aerosol. Additionally, the scattering matrix of cypress pollen has been measured and extrapo- lated to explore differences with mineral dust that can be exploited in atmospheric detection. Field mea- surements of the backscattering linear depolarization ratio δL (180 °) are used to obtain information about non-sphericity and discrimination between fine and coarse aerosol. However, the average δL (180 °) for the three types of aerosols considered in this work in the visible spectral range is δL (180 °) = 0.40 ±0.05. This shows that δL (180 °) is not informative about the composition or morphology of irregular particles. By contrast, measurements of scattering matrix elements or depolarization ratios at different scattering angles may provide information about the structural differences of particles, and in particular may en- able to differentiate airborne volcanic ash from desert dust, which are otherwise similar in terms of size and optical constants. Cypress pollen shows a characteristic degree of linear polarization curve that is very different from that of polydisperse irregular mineral dust. Light scattering field instruments and re- mote sensing methods could extract more information about the characteristics of aerosol particles if modifications were introduced to measure the phase curves of several scattering matrix elements or de- polarization ratios.excellence research program of the Andalusian Regional Government P18RT-1854National Plan of Scientific and Technical Research and Innovation of the Spanish Ministry of Science and Innovation RTI2018-095330-B-100Spanish State Agency for Research SEV-2017-0709Spanish Government RYC-2016-1957

Newly rare or newly common: evolutionary feedbacks through changes in population density and relative species abundance, and their management implications

Environmental management typically seeks to increase or maintain the population sizes of desirable species and to decrease population sizes of undesirable pests, pathogens, or invaders. With changes in population size come long-recognized changes in ecological processes that act in a density-dependent fashion. While the ecological effects of density dependence have been well studied, the evolutionary effects of changes in population size, via changes in ecological interactions with community members, are underappreciated. Here, we provide examples of changing selective pressures on, or evolution in, species as a result of changes in either density of conspecifics or changes in the frequency of heterospecific versus conspecific interactions. We also discuss the management implications of such evolutionary responses in species that have experienced rapid increases or decreases in density caused by human actions

MicroRNA Predictors of Longevity in Caenorhabditis elegans

Neither genetic nor environmental factors fully account for variability in individual longevity: genetically identical invertebrates in homogenous environments often experience no less variability in lifespan than outbred human populations. Such variability is often assumed to result from stochasticity in damage accumulation over time; however, the identification of early-life gene expression states that predict future longevity would suggest that lifespan is least in part epigenetically determined. Such “biomarkers of aging,” genetic or otherwise, nevertheless remain rare. In this work, we sought early-life differences in organismal robustness in unperturbed individuals and examined the utility of microRNAs, known regulators of lifespan, development, and robustness, as aging biomarkers. We quantitatively examined Caenorhabditis elegans reared individually in a novel apparatus and observed throughout their lives. Early-to-mid–adulthood measures of homeostatic ability jointly predict 62% of longevity variability. Though correlated, markers of growth/muscle maintenance and of metabolic by-products (“age pigments”) report independently on lifespan, suggesting that graceful aging is not a single process. We further identified three microRNAs in which early-adulthood expression patterns individually predict up to 47% of lifespan differences. Though expression of each increases throughout this time, mir-71 and mir-246 correlate with lifespan, while mir-239 anti-correlates. Two of these three microRNA “biomarkers of aging” act upstream in insulin/IGF-1–like signaling (IIS) and other known longevity pathways, thus we infer that these microRNAs not only report on but also likely determine longevity. Thus, fluctuations in early-life IIS, due to variation in these microRNAs and from other causes, may determine individual lifespan

The SPIRITS Sample of Luminous Infrared Transients: Uncovering Hidden Supernovae and Dusty Stellar Outbursts in Nearby Galaxies

We present a systematic study of the most luminous (M IR [Vega magnitudes] brighter than −14) infrared (IR) transients discovered by the SPitzer InfraRed Intensive Transients Survey (SPIRITS) between 2014 and 2018 in nearby galaxies (D 12) show multiple, luminous IR outbursts over several years and have directly detected, massive progenitors in archival imaging. With analyses of extensive, multiwavelength follow-up, we suggest the following possible classifications: five obscured core-collapse supernovae (CCSNe), two erupting massive stars, one luminous red nova, and one intermediate-luminosity red transient. We define a control sample of all optically discovered transients recovered in SPIRITS galaxies and satisfying the same selection criteria. The control sample consists of eight CCSNe and one Type Iax SN. We find that 7 of the 13 CCSNe in the SPIRITS sample have lower bounds on their extinction of 2 < A V < 8. We estimate a nominal fraction of CCSNe in nearby galaxies that are missed by optical surveys as high as ${38.5}_{-21.9}^{+26.0} \%$ (90% confidence). This study suggests that a significant fraction of CCSNe may be heavily obscured by dust and therefore undercounted in the census of nearby CCSNe from optical searches

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio