Extraordinary human energy consumption and resultant geological impacts beginning around 1950 CE initiated the proposed Anthropocene Epoch

Growth in fundamental drivers—energy use, economic productivity and population—can provide quantitative indications of the proposed boundary between the Holocene Epoch and the Anthropocene. Human energy expenditure in the Anthropocene, ~22 zetajoules (ZJ), exceeds that across the prior 11,700 years of the Holocene (~14.6 ZJ), largely through combustion of fossil fuels. The global warming effect during the Anthropocene is more than an order of magnitude greater still. Global human population, their productivity and energy consumption, and most changes impacting the global environment, are highly correlated. This extraordinary outburst of consumption and productivity demonstrates how the Earth System has departed from its Holocene state since ~1950 CE, forcing abrupt physical, chemical and biological changes to the Earth’s stratigraphic record that can be used to justify the proposal for naming a new epoch—the Anthropocene

SREBP-2/PNPLA8 axis improves non-alcoholic fatty liver disease through activation of autophagy

Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride. Moreover, we show that over-expression of PNPLA8 dramatically decreases hepatic steatosis through increased autophagy in hepatocytes of HFD-fed mice. Live-cell imaging analyses also reveal that PNPLA8 dynamically interacts with LC3 and we suggest that the SREBP-2/PNPLA8 axis represents a novel regulatory mechanism for lipid homeostasis. These data provide a possible mechanism for the reported beneficial effects of statins for decreasing hepatic triglyceride levels in NAFLD patients.ope

A Locked Nucleic Acid Antisense Oligonucleotide (LNA) Silences PCSK9 and Enhances LDLR Expression In Vitro and In Vivo

The proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important factor in the etiology of familial hypercholesterolemia (FH) and is also an attractive therapeutic target to reduce low density lipoprotein (LDL) cholesterol. PCSK9 accelerates the degradation of hepatic low density lipoprotein receptor (LDLR) and low levels of hepatic PCSK9 activity are associated with reduced levels of circulating LDL-cholesterol.The present study presents the first evidence for the efficacy of a locked nucleic acid (LNA) antisense oligonucleotide (LNA ASO) that targets both human and mouse PCSK9. We employed human hepatocytes derived cell lines HepG2 and HuH7 and a pancreatic mouse beta-TC3 cell line known to express high endogenous levels of PCSK9. LNA ASO efficiently reduced the mRNA and protein levels of PCSK9 with a concomitant increase in LDLR protein levels after transfection in these cells. In vivo efficacy of LNA ASO was further investigated in mice by tail vein intravenous administration of LNA ASO in saline solution. The level of PCSK9 mRNA was reduced by approximately 60%, an effect lasting more than 16 days. Hepatic LDLR protein levels were significantly up-regulated by 2.5-3 folds for at least 8 days and approximately 2 fold for 16 days. Finally, measurement of liver alanine aminotransferase (ALT) levels revealed that long term LNA ASO treatment (7 weeks) does not cause hepatotoxicity.LNA-mediated PCSK9 mRNA inhibition displayed potent reduction of PCSK9 in cell lines and mouse liver. Our data clearly revealed the efficacy and safety of LNA ASO in reducing PCSK9 levels, an approach that is now ready for testing in primates. The major significance and take home message of this work is the development of a novel and promising approach for human therapeutic intervention of the PCSK9 pathway and hence for reducing some of the cardiovascular risk factors associated with the metabolic syndrome

Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities

<p>Abstract</p> <p>Background</p> <p>PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity.</p> <p>Results</p> <p>We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls.</p> <p>Conclusion</p> <p>We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.</p

Galectin-1 Is Part of Human Trophoblast Invasion Machinery - A Functional Study In Vitro

Interactions of glycoconjugates with endogenous galectins, have been long proposed to participate in several reproductive processes including implantation. In human placenta gal-1, gal-3, gal-8, and gal-13 proteins are known to be present. Each of them has been proposed to play multiple functions, but so far no clear picture has emerged. We hypothesized that gal-1 participates in trophoblast invasion, and conducted Matrigel invasion assay using isolated cytotrophoblast from first trimester placenta and HTR-8/SVneo cell line to test it.<0.001) by Ox-gal-1 at 1 µg/ml. Both sets of results confirmed involvement of gal-1 in trophoblast invasion. Galectin profile of isolated cytotrophoblast and HTR-8/SVneo cells was established using RT-PCR and real-time PCR and found to consist of gal-1, gal-3 and gal-8 for both cell types. Only gal-1 was located at the trophoblast cell membrane, as determined by FACS analysis, which is consistent with the results of the functional tests.These findings qualify gal-1 as a member of human trophoblast cell invasion machinery

Patient Discomfort Associated with the Use of Intra-arterial Iodinated Contrast Media: A Meta-Analysis of Comparative Randomized Controlled Trials

<p>Abstract</p> <p>Background</p> <p>Discomfort characterized by pain and warmth are common adverse effects associated with the use of intra-arterial iodinated contrast media (CM). The objective of this review was to pool patient-reported outcomes available from head-to-head randomized controlled trials (RCTs) and to compare the discomfort rates associated with iso-osmolar contrast media (IOCM; i.e., iodixanol) to those reported with various low-osmolar contrast media (LOCM).</p> <p>Methods</p> <p>A review of the literature published between 1990 and 2009 available through Medline, Medline Preprints, Embase, Biological Abstracts, BioBase, Cab Abstracts, International Pharmaceutical Abstracts, Life Sciences Collection, Inside Conferences, Energy Database, Engineering Index and Technology Collection was performed to compare rates of discomfort associated with the use of the IOCM (iodixanol) vs. various LOCM agents in head-to-head RCTs. All trials with a Jadad score ≥2 that reported patient discomfort data following intra-arterial administration of CM were reviewed, coded, and extracted.</p> <p>Results</p> <p>A total of 22 RCTs (n = 8087) were included. Overall discomfort (regardless of severity) was significantly different between patients receiving IOCM and various LOCMs (risk difference [RD] -0.049; 95% confidence interval [CI]: -0.076, -0.021; p = 0.001). IOCM was favored over all LOCMs combined with a summary RD value of -0.188 (95% CI: -0.265, -0.112; p < 0.001) for incidence of pain, regardless of severity. A greater reduction in the magnitude of pain was observed with IOCM (iodixanol), particularly with selective limb and carotid/intracerebral procedures. Similarly, the meta-analysis of warmth sensation, regardless of severity, favored IOCM over LOCMs with an RD of -0.043 (95% CI: -0.074, -0.011; p = 0.008). A positive linear relationship was observed between the discomfort effect size and age and a negative relationship with increasing proportion of women. The opposite trends were observed with warmth sensation.</p> <p>Conclusions</p> <p>IOCM was associated with less frequent and severe patient discomfort during intra-arterial administration. These data support differences in osmolality as a possible determinant of CM discomfort.</p

Adult-Young Ratio, a Major Factor Regulating Social Behaviour of Young: A Horse Study

Adults play an important role in regulating the social behaviour of young individuals. However, a few pioneer studies suggest that, more than the mere presence of adults, their proportions in social groups affect the social development of young. Here, we hypothesized that aggression rates and social cohesion were correlated to adult-young ratios. Our biological model was naturally-formed groups of Przewalski horses, Equus f. przewalskii, varying in composition.We investigated the social interactions and spatial relationships of 12 one- and two-year-old Przewalski horses belonging to five families with adult-young ratios (AYR) ranging from 0.67 to 1.33. We found striking variations of aggression rates and spatial relationships related to the adult-young ratio: the lower this ratio, the more the young were aggressive, the more young and adults segregated and the tighter the young bonded to other young.This is the first study demonstrating a correlation between adult-young ratios and aggression rates and social cohesion of young individuals in a naturalistic setting. The increase of aggression and the emergence of social segregation in groups with lower proportions of adults could reflect a related decrease of the influence of adults as regulators of the behaviour of young. This social regulation has both theoretical and practical implications for understanding the modalities of the influence of adults during ontogeny and for recommending optimal settings, as for instance, for schooling or animal group management

Metabolic syndrome and carotid intima-media thickness in chronic obstructive pulmonary disease

BACKGROUND: The aim of this study is to investigate the prevalence of metabolic syndrome (MetS), carotid intima media thickness (IMT), and serum C-reactive protein (CRP) levels in patients with chronic obstructive pulmonary disease (COPD), and the possible relationships among them. METHODS: Fifty stable COPD patients and 40 healthy controls were included in the study. The participants were further divided into four groups according to their smoking status. Pulmonary function tests were performed in COPD patients. Anthropometric measurements and blood chemistry analysis, serum CRP levels and carotid intima-media thickness (IMT) measurements were performed in all the study population. RESULTS: Prevalence of metabolic syndrome was 43% in COPD patients and 30% in the control group (p = 0.173). FEV(1)% and FEV(1)/FVC were higher in COPD patients with MetS (p = 0.001 and p = 0.014, respectively) compared to those without MetS. Prevalence of MetS was significantly different among the COPD patients with different stages (p = 0.017) with the highest value in stage 2 (59%). Carotid IMT was significantly higher in COPD patients than in control group (1.07 ± 0.25 mm and 0.86 ± 0.18 mm, respectively; p < 0.001). Serum CRP levels were not different in COPD patients and controls, however they were higher in individuals with MetS compared to those without MetS regardless of COPD presence (p = 0.02). CONCLUSIONS: Early markers of atherogenesis, in terms of carotid IMT, were found to be higher in COPD patients than in healthy controls. MetS prevalence was observed to decrease as the severity of airflow obstruction increased. Therefore, screening COPD patients for these cardiovascular risk factors would be a novel approach even in absence of symptoms

An eye-movement study of relational memory in adults with Autism Spectrum Disorder

Persons with Autism Spectrum Disorder (ASD) demonstrate good memory for single items but difficulties remembering contextual information related to these items. Recently, we found compromised explicit but intact implicit retrieval of object-location information in ASD (Ring et al. 2015). Eye-movement data collected from a sub-sample of the participants are the focus of the current paper. At encoding, trial-by-trial viewing durations predicted subsequent retrieval success only in typically developing (TD) participants. During retrieval, TD compared to ASD participants looked significantly longer at previously studied objectlocations compared to alternative locations. These findings extend similar observations recently reported by Cooper et al. (2017a) and demonstrate that eye-movement data can shed important light on the source and nature of relational memory difficulties in ASD