Angiopoietin-like protein 3, an emerging cardiometabolic therapy target with systemic and cell-autonomous functions

Angiopoietin like protein 3 (ANGPTL3) is best known for its function as an inhibitor of lipoprotein and endothelial lipases. Due to the capacity of genetic or pharmacologic ANGPTL3 suppression to markedly reduce circulating lipoproteins, and the documented cardioprotection upon such suppression, ANGPTL3 has become an emerging therapy target for which both antibody and antisense oligonucleotide (ASO) therapeutics are being clinically tested. While the antibody is relatively selective for circulating ANGPTL3, the ASO also depletes the intra-hepatocellular protein, and there is emerging evidence for cell-autonomous functions of ANGPTL3 in the liver. These include regulation of hepatocyte glucose and fatty acid uptake, insulin sensitivity, LDL/VLDL remnant uptake, VLDL assembly/secretion, polyunsaturated fatty acid (PUFA) and PUFA-derived lipid mediator content, and gene expression. In this review we elaborate on (i) why ANGPTL3 is considered one of the most promising new cardiometabolic therapy targets, and (ii) the present evidences for its intra-hepatocellular or cell-autonomous functions.Peer reviewe

Koneoppiminen:ohjattu oppiminen taloustieteellisessä tutkimuksessa

Tiivistelmä. Tämän tutkielman tarkoituksena on selvittää, voitaisiinko koneoppimista hyödyntää taloustieteellisessä tutkimuksessa. Koneoppiminen on saavuttanut viime vuosina suurta suosiota ja koneoppimista on sovellettu lukuisten erilaisten ongelmien ratkaisemiseksi. Viime vuosina myös taloustieteilijöiden keskuudessa on alkanut herätä mielenkiintoa koneoppimista kohtaan. Koneoppiminen voidaan jakaa kahteen osa-alueeseen: ohjattuun oppimiseen ja ohjaamattomaan oppimiseen. Ohjatun oppimisen ja perinteisten ekonometrian menetelmien tavoite on periaatteessa sama ja ohjatun oppimisen menetelmiä voitaisiinkin mahdollisesti soveltaa tutkimuskäytössä perinteisten ekonometrian menetelmien tapaan. Tutkielman teoria osuudessa käsitellään koneoppimisen keskeisiä perusperiaatteita sekä useiden koneoppimismenetelmien toimintaperiaatteita. Teoria osuudessa käsitellään lisäksi koneoppimisen ja perinteisten ekonometrian menetelmien eroja sekä mitä ongelmia koneoppimismenetelmiin liittyy. Koneoppimisen paremmuutta perinteisiin tilastollisiin menetelmiin verrattuna perustellaan niiden paremmalla ennustamiskyvyllä. Koneoppimismenetelmien avulla voidaan sovittaa aineistoihin hyvinkin monimutkaisia malleja ja niiden avulla voidaan aineistosta löytää rakenteita, joita ei perinteisten menetelmien avulla voida löytää. Koneoppimisen soveltamisessa tutkimuskäyttöön liittyy kuitenkin joitain ongelmia. Yksi keskeinen ongelma on se, että koneoppimismenetelmiä ei ole suunniteltu syy-seuraussuhteiden selvittämiseen vaan ne on suunniteltu puhtaasti ennustamistarkoitukseen. Viime aikoina on kuitenkin pyritty kehittämään uusia koneoppimismenetelmiä, joiden avulla voidaan estimoida myös syy-seuraussuhteita. Tutkielman empiirisessä osuudessa vertaillaan koneoppimismenetelmiä sekä ekonometriassa perinteisesti käytettävää logistista regressiota. Empiirisessä osuudessa pyrittiin ennustamaan portugalilaisen pankin asiakkaiden käytöstä. Empiirisen osuuden lopputulokseksi saatiin se, että koneoppimismallit eivät olleet merkittävästi parempia ennustamaan kuin logistinen regressiokaan. Tutkielman tuloksena voidaan sanoa, että koneoppimista voidaan hyödyntää taloustieteellisessä tutkimuksessa. Mutta kuten tutkielman empiirisestä osuudesta nähdään, niin koneoppimismenetelmät eivät välttämättä ole joka tilanteessa perinteisiä regressiomalleja parempia. Suurin potentiaalinen käyttökohde koneoppimiselle onkin suurten tietoaineistojen eli niin sanotun big datan analysointi

Own or shared silage feeding place for dairy cows?

We studied behaviour, silage eating and milk production of cows when every animal had an own silage feeding place and when the feeding place was shared with two other cows

Cultivating resilience by empirically revealing response diversity

201

High heterotrophic CO2 emissions from a Malaysian oil palm plantations during dry-season

Background Tropical peatlands are currently being rapidly cleared and drained for the establishment of oil palm plantations, which threatens their globally significant carbon sequestration capacity. Large-scale land conversion of tropical peatlands is important in the context of greenhouse gas emission factors and sustainable land management. At present, quantification of carbon dioxide losses from tropical peatlands is limited by our understanding of the relative contribution of heterotrophic and autotrophic respiration to net peat surface CO2 emissions. Methods In this study we separated heterotrophic and autotrophic components of peat CO2 losses from two oil palm plantations (one established in ‘2000’ and the other in 1978, then replanted in ‘2006’) using chamber-based emissions sampling along a transect from the rooting to non-rooting zones on a peatland in Selangor, Peninsular Malaysia over the course of three months (June-August, 2014). Collar CO2 measurements were compared with soil temperature and moisture at site and also accompanied by depth profiles assessing peat C and bulk density. Results The soil respiration decreased exponentially with distance from the palm trunks with the sharpest decline found for the plantation with the younger palms. The mean heterotrophic flux was 1244.7 ± SE 149.2 mg m-2h-1 and 663.8 ± SE 102.2 mg m-2h-1 at the 2000 and 2006 plantations, respectively. Autotrophic emissions adjacent to the palm trunks were 944 ± SE 99.7 mg m-2h-1 and 1962 ± SE 246 mg m-2h-1 at the 2000 and 2006 plantations, respectively. Heterotrophic CO2 flux was positively related to peat soil moisture, but not temperature. Total peat C stocks were 60 kg m-2 (down to 1 m depth) and did not vary among plantations of different ages but SOC concentrations declined significantly with depth at both plantations but the decline was sharper in the second generation 2006 plantation. Conclusions The CO2 flux values reported in this study suggest a potential for very high carbon (C) loss from drained tropical peats during the dry season. This is particularly concerning given that more intense dry periods related to climate change are predicted for SE Asia. Taken together, this study highlights the need for careful management of tropical peatlands, and the vulnerability of their carbon storage capability under conditions of drainage

Classification des potentiels évoqués par corrélation de Pearson dans une interface cerveau-ordinateur

National audienceDans cette communication, nous décrivons et évaluons les performances d'une technique d'apprentissage des coefficients d'un classifieur linéaire utilisé dans une interface cerveau-ordinateur. Les signaux de l'électroencéphalogramme d'un individu sont analysés au moyen de cette technique afin de mettre en évidence les réponses de ce dernier à des stimuli visuels. Le traitement et la classification des signaux sont utilisés afin d'implanter un système de communication palliative permettant à l'individu d'épeler des mots. Les performances de la méthode de classification ont été évaluées par une expérimentation sur huit personnes

Milk and milk-derived peptides combat against hypertension and vascular dysfunction : a review

Epidemiological studies have revealed that consumption of milk and fermented dairy products is inversely associated with elevated blood pressure and with many of the risk factors of the metabolic syndrome. Previously, calcium was thought to be behind this phenomenon, but during the last 20 years, convincing evidence emerging from experimental, epidemiological and intervention studies has highlighted the important role of the small peptides formed during fermentation processes. This review provides an overview of the potential blood pressure lowering components present in dairy products with a special focus on casein-derived tripeptides.Peer reviewe

High potential for weathering and climate effects of non-vascular vegetation in the Late Ordovician

It has been hypothesized that predecessors of today’s bryophytes significantly increased global chemical weathering in the Late Ordovician, thus reducing atmospheric CO2 concentration and contributing to climate cooling and an interval of glaciations. Studies that try to quantify the enhancement of weathering by non-vascular vegetation, however, are usually limited to small areas and low numbers of species, which hampers extrapolating to the global scale and to past climatic conditions. Here we present a spatially explicit modelling approach to simulate global weathering by non-vascular vegetation in the Late Ordovician. We estimate a potential global weathering flux of 2.8 (km3 rock) yr−1, defined here as volume of primary minerals affected by chemical transformation. This is around three times larger than today’s global chemical weathering flux. Moreover, we find that simulated weathering is highly sensitive to atmospheric CO2 concentration. This implies a strong negative feedback between weathering by non-vascular vegetation and Ordovician climate

Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles

High-density lipoproteins (HDLs) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway. Importantly, changes in the protein and lipid composition of HDLsmay lead to the formation of particles with reduced atheroprotective properties. Here, we show that Streptococcus pneumoniae pneumolysin (PLY) and neuraminidase A (NanA) impair HDL function by causing chemical and structural modifications of HDLs. The proteomic, lipidomic, cellular, and biochemical analysis revealed that PLY and NanA induce significant changes in sialic acid, protein, and lipid compositions of HDL. The modified HDL particles have reduced cholesterol acceptor potential from activated macrophages, elevated levels of malondialdehyde adducts, and show significantly increased complement activating capacity. These results suggest that accumulation of these modified HDL particles in the arterial intima may present a trigger for complement activation, inflammatory response, and thereby promote atherogenic disease progression.Peer reviewe

CO2 fertilization of Sphagnum peat mosses is modulated by water table level and other environmental factors

Sphagnum mosses account for most accumulated dead organic matter in peatlands. Therefore, understanding their responses to increasing atmospheric CO2 is needed for estimating peatland C balances under climate change. A key process is photorespiration: a major determinant of net photosynthetic C assimilation that depends on the CO2 to O-2 ratio. We used climate chambers to investigate photorespiratory responses of Sphagnum fuscum hummocks to recent increases in atmospheric CO2 (from 280 to 400 ppm) under different water table, temperature, and light intensity levels. We tested the photorespiratory variability using a novel method based on deuterium isotopomers (D6(S)/D6(R) ratio) of photosynthetic glucose. The effect of elevated CO2 on photorespiration was highly dependent on water table. At low water table (-20 cm), elevated CO2 suppressed photorespiration relative to C assimilation, thus substantially increasing the net primary production potential. In contrast, a high water table (similar to 0 cm) favored photorespiration and abolished this CO2 effect. The response was further tested for Sphagnum majus lawns at typical water table levels (similar to 0 and -7 cm), revealing no effect of CO2 under those conditions. Our results indicate that hummocks, which typically experience low water table levels, benefit from the 20th century's increase in atmospheric CO2