505 research outputs found
Emerging roles of SIRT1 in vascular endothelial homeostasis
Sir2 is a NAD(+)-dependent deacetylase, which regulates life span in multiple model organisms in response to caloric restriction. Mammalian homologues of Sir2 comprise a family of seven proteins termed sirtuins (SIRT1-SIRT7), which have gained considerable attention for their impact on several important physiological processes associated with metabolism and stress resistance. In addition, recent studies point to SIRT1 as a key regulator of vascular endothelial homeostasis controlling angiogenesis, vascular tone and endothelial dysfunction. Here, we review the emerging role of SIRT1 as an important modulator of signaling networks critical for maintaining vascular endothelial homeostasis and discuss SIRT1 as a potential therapeutic target for cardiovascular diseases in the adult
The multiplicative effect of combining alcohol with energy drinks on adolescent gambling
Purpose: There has been increased concern about the negative effects of adolescents consuming a combination of alcohol mixed with energy drinks (AmED). To date, few studies have focused on AmED use and gambling. The present study analyzed the multiplicative effect of AmED consumption, compared to alcohol alone, on the likelihood of at-risk or problem gambling during adolescence.
Methods: Data from the ESPAD®Italia 2015 study, a cross-sectional survey conducted in a nationally representative sample of students (ages 15 to 19 years) were used to examine the association between self-reported AmED use (≥ 6 times, ≥ 10 times, and ≥ 20 times during the last month) and self-reported gambling severity. Multivariate models were used to calculate adjusted prevalence ratios to evaluate the association between alcohol use, AmED use, and gambling among a representative sample of adolescents who reported gambling in the last year and completed a gambling severity scale (n = 4495).
Results: Among the 19% students classed as at-risk and problem gamblers, 43.9% were classed as AmED consumers, while 23.6% were classed as alcohol consumers (i.e. did not mix alcohol with energy drinks). In multivariate analyses that controlled for covariates, AmED consumers were three times more likely to be at-risk and problem gamblers (OR = 3.05) compared to non-consuming adolescents, while the effect became less pronounced with considering those who consumed alcohol without the addition of energy drinks (OR = 1.37).
Conclusions: The present study clearly established that consuming AmED might pose a significantly greater risk of experiencing gambling-related problems among adolescents
Fruit quality characterization of new sweet cherry cultivars as a good source of bioactive phenolic compounds with antioxidant and neuroprotective potential
Sweet cherries (Prunus avium L.) are highly appreciated fruits for their taste, color, nutritional value, and beneficial health effects. In this work, seven new cultivars of sweet cherry were investigated for their main quality traits and nutraceutical value. The phytochemical profile of three classes of phenolic compounds and the antioxidant activity of the new cultivars were investigated through high-performance liquid chromatography with diode array detection (HPLC-DAD) and spectrophotometric assays, respectively, and compared with those of commonly commercialized cultivars. Cyanidine-3-O-rutinoside was the main anthocyanin in all genotypes, and its levels in some new cultivars were about three-fold higher than in commercial ones. The ORAC-assayed antioxidant capacity was positively correlated with the total anthocyanin index. The nutraceutical value of the new cultivars was investigated in terms of antioxidant/neuroprotective capacity in neuron-like SH-SY5Y cells. Results demonstrated that the new cultivars were more effective in counteracting oxidative stress and were also able to upregulate brain-derived neurotrophic factor (BDNF), a pro-survival neurotrophin, suggesting their potential pleiotropic role in counteracting neurodegenerations
Compatible and incompatible pollen-styles interaction in Pyrus communis l. Show different transglutaminase features, polyamine pattern and metabolomics profiles
Pollen-stigma interaction is a highly selective process, which leads to compatible or incompatible pollination, in the latter case, affecting quantitative and qualitative aspects of productivity in species of agronomic interest. While the genes and the corresponding protein partners involved in this highly specific pollen-stigma recognition have been studied, providing important insights into pollen-stigma recognition in self-incompatible (SI), many other factors involved in the SI response are not understood yet. This work concerns the study of transglutaminase (TGase), polyamines (PAs) pattern and metabolomic profiles following the pollination of Pyrus communis L. pistils with compatible and SI pollen in order to deepen their possible involvement in the reproduction of plants. Immunolocalization, abundance and activity of TGase as well as the content of free, soluble-conjugated and insoluble-bound PAs have been investigated. 1H NMR-profiling coupled with multivariate data treatment (PCA and PLS-DA) allowed to compare, for the first time, the metabolic patterns of not-pollinated and pollinated styles. Results clearly indicate that during the SI response TGase activity increases, resulting in the accumulation of PAs conjugated to hydroxycinnamic acids and other small molecules. Metabolomic analysis showed a remarkable differences between pollinated and not-pollinated styles, where, except for glucose, all the other metabolites where less concentrated. Moreover, styles pollinated with compatible pollen showed the highest amount of sucrose than SI pollinated ones, which, in turn, contained highest amount of all the other metabolites, including aromatic compounds, such as flavonoids and a cynnamoil derivative
A complexityoriented approach to global production network design in:
Abstract-The structure of production networks has become more and more complex due to the growth of companies by acquisitions and set ups of production plants to enter new markets. In this paper, we present an approach to design production networks with a minimum level of structural complexity in order to keep up the operability of such networks. The approach consists of three basic elements, all embedded into an optimization algorithm: the capture of structural complexity via characteristic parameters, the determination of causal relations between those parameters and the development of a complexity indicator. Using a data set of a recently conducted industry project, we show that our method is beneficial for the optimization of production networks. Index Terms-complexity measurement, complexity oriented design, optimization algorithm, production networks
Forensic, legal, and clinical aspects of deaths associated with implanted cardiac devices
As the population ages, the prevalence of heart failure and individuals wearing an
implanted cardiac device is increasing. The combination of different underlying
pathophysiologies and (the combination of) implanted cardiac devices can
become a challenge with regard to the determination of cause and manner of
death in such individuals. Additionally, heart disease is frequently associated with
mental disease, ranging from anxiety and depression to suicidality and suicide
(attempts). At the same time, the correct diagnosis of cause and manner of death
is the basis for quality assurance, further therapeutic advances, legal safety, and
suicide prevention. By that, an interdisciplinary field between legal medicine,
clinicians, and law enforcement opens up. In this field, the different participants
can simultaneously benefit from and need each other. For example, legal medicine
experts need investigatory results and clinical expertise for the interpretation of
readout data of implanted cardiac devices in order to correctly determine the
cause of death. A correctly determined cause of death can assist law enforcement
and help clinicians to further improve various therapeutic approaches based on
correct mortality data collection. In addition, it is the basis for identification of
suicides of device carriers, allowing psychological and psychiatric experts to
better understand the burden of mental disease in this particular cohort. Against
this interdisciplinary background, this manuscript summarizes information about
psychiatric comorbidities and suicidality while being on a device. Thereby, basic
information on complications and malfunctions of implanted cardiac devices,
device-associated deaths with particular emphasis on device manipulation is
displayed as basic information needed for correct determination of the cause
of death. Also, legal and ethical issues in this field are outlined. The final result is
a proposal of an interdisciplinary assessment workflow for a conjoint approach
to improve the diagnosis of deaths associated with implanted cardiac devices. It
will allow for a differentiation between an individual who died with or due to the
device
PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
Coordinated activity of VEGF and Notch signals guides the endothelial cell (EC) specification into tip and stalk cells during angiogenesis. Notch activation in stalk cells leads to proliferation arrest via an unknown mechanism. By using gain- and loss-of-function gene-targeting approaches, here we show that PTEN is crucial for blocking stalk cell proliferation downstream of Notch, and this is critical for mouse vessel development. Endothelial deletion of PTEN results in vascular hyperplasia due to a failure to mediate Notch-induced proliferation arrest. Conversely, overexpression of PTEN reduces vascular density and abrogates the increase in EC proliferation induced by Notch blockade. PTEN is a lipid/protein phosphatase that also has nuclear phosphatase-independent functions. We show that both the catalytic and non-catalytic APC/C-Fzr1/Cdh1-mediated activities of PTEN are required for stalk cells' proliferative arrest. These findings define a Notch-PTEN signalling axis as an orchestrator of vessel density and implicate the PTEN-APC/C-Fzr1/Cdh1 hub in angiogenesis
Regional specialization and fate specification of bone stromal cells in skeletal development
Bone stroma contributes to the regulation of osteogenesis and hematopoiesis but also to fracture healing and disease processes. Mesenchymal stromal cells from bone (BMSCs) represent a heterogenous mixture of different subpopulations with distinct molecular and functional properties. The lineage relationship between BMSC subsets and their regulation by intrinsic and extrinsic factors are not well understood. Here, we show with mouse genetics, ex vivo cell differentiation assays, and transcriptional profiling that BMSCs from metaphysis (mpMSCs) and diaphysis (dpMSCs) are fundamentally distinct. Fate-tracking experiments and single-cell RNA sequencing indicate that bone-forming osteoblast lineage cells and dpMSCs, including leptin receptor-positive (LepR(+)) reticular cells in bone marrow, emerge from mpMSCs in the postnatal metaphysis. Finally, we show that BMSC fate is controlled by platelet-derived growth factor receptor β (PDGFRβ) signaling and the transcription factor Jun-B. The sum of our findings improves our understanding of BMSC development, lineage relationships, and differentiation
The complex TIE between macrophages and angiogenesis
Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway
Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells
The regulation of acetylation is central for the epigenetic control of lineage-specific gene expression and determines cell fate decisions. We provide evidence that the inhibition of histone deacetylases (HDACs) blocks the endothelial differentiation of adult progenitor cells. To define the mechanisms by which HDAC inhibition prevents endothelial differentiation, we determined the expression of homeobox transcription factors and demonstrated that HoxA9 expression is down-regulated by HDAC inhibitors. The causal involvement of HoxA9 in the endothelial differentiation of adult progenitor cells is supported by the finding that HoxA9 overexpression partially rescued the endothelial differentiation blockade induced by HDAC inhibitors. Knockdown and overexpression studies revealed that HoxA9 acts as a master switch to regulate the expression of prototypical endothelial-committed genes such as endothelial nitric oxide synthase, VEGF-R2, and VE-cadherin, and mediates the shear stress–induced maturation of endothelial cells. Consistently, HoxA9-deficient mice exhibited lower numbers of endothelial progenitor cells and showed an impaired postnatal neovascularization capacity after the induction of ischemia. Thus, HoxA9 is regulated by HDACs and is critical for postnatal neovascularization
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