The deployment of conditional probability distributions for death time estimation

The temperature based algorithm known as the Nomogram Method for the determination of a 95.45% death-time interval can be combined with non-temperature based (NTB) findings in the so called Compound Method (CM). The impact of such integration on the probability yielded by the resulting interval has however neither been described nor exploited. In fact the interval after integration of NTB findings rarely yields 95.45% probability. We present a technique, based on the conditional probability distribution that can be calculated if the NTB findings are taken into account, which ensures the probability inside the interval to be 95.45%. The technique was successfully applied to a set of 53 cases published by Henssge et al. and led to a reduction of the interval width up to more than 15% compared to the CM interval, whereas in other cases the interval width increased due to probability content of the CM intervals below 95.45%. A spreadsheet file in which the method proposed in this paper is implemented can be obtained upon email request from the author S. Potent

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

Pulsed led light: Exploring the balance between energy use and nutraceutical properties in indoor-grown lettuce

In indoor vertical farms, energy consumption represents a bottleneck for both a system\u2019s affordability and environmental footprint. Although switching frequency (sf) represents a crucial factor in determining the efficacy of light emitting diodes (LED) lighting systems in converting electricity into light, the impact of sf is still underexplored. The aim of this work was to investigate the effect of LEDs sf on the productive and qualitative responses of lettuce (Lactuca sativa L.), also considering the resource use efficiency. Plants were grown for 14 days under red and blue LEDs (215 \u3bcmol m 122 s 121 and 16/8 h light/dark, with a red:blue ratio of 3) characterized by two different sf for the blue diode, namely high sf (850 kHz) and low sf (293 kHz). A fluorescent light (same light intensity and photoperiod) was included. LED sf did not alter plant morphological parameters, including fresh or dry biomass, leaf number, leaf area, or water use efficiency. A low sf increased the energy use efficiency (EUE) by 40% as compared to high sf. The latter enhanced the leaf antioxidant capacity, as a consequence of increased concentrations of caftaric and chicoric acids, isoquercetin, and luteolin, consistent with the upregulation of a few genes related to the biosynthetic pathway of phenolic compounds (4C3H and DFR). The study highlights that different sf may significantly affect the EUE as well as crop nutritional properties

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

Downregulation of the Longevity-Associated Protein Sirtuin 1 in Insulin Resistance and Metabolic Syndrome: Potential Biochemical Mechanisms

OBJECTIVE: Sirtuins (SIRTs) are NAD(+)-dependent deacetylases that regulate metabolism and life span. We used peripheral blood mononuclear cells (PBMCs) to determine ex vivo whether insulin resistance/metabolic syndrome influences SIRTs. We also assessed the potential mechanisms linking metabolic alterations to SIRTs in human monocytes (THP-1) in vitro. RESEARCH DESIGN AND METHODS: SIRT1-SIRT7 gene and protein expression was determined in PBMCs of 54 subjects (41 with normal glucose tolerance and 13 with metabolic syndrome). Insulin sensitivity was assessed by the minimal model analysis. Subclinical atherosclerosis was assessed by carotid intima-media thickness (IMT). In THP-1 cells exposed to high glucose or fatty acids in vitro, we explored SIRT1 expression, p53 acetylation, Jun NH(2)-terminal kinase (JNK) activation, NAD(+) levels, and nicotinamide phosphoribosyltransferase (NAMPT) expression. The effects of SIRT1 induction by resveratrol and of SIRT1 gene silencing were also assessed. RESULTS: In vivo, insulin resistance and metabolic syndrome were associated with low PBMC SIRT1 gene and protein expression. SIRT1 gene expression was negatively correlated with carotid IMT. In THP-1 cells, high glucose and palmitate reduced SIRT1 and NAMPT expression and reduced the levels of intracellular NAD(+) through oxidative stress. No effect was observed in cells exposed to linoleate or insulin. High glucose and palmitate increased p53 acetylation and JNK phosphorylation; these effects were abolished in siRNA SIRT1-treated cells. Glucose- and palmitate-mediated effects on NAMPT and SIRT1 were prevented by resveratrol in vitro. CONCLUSIONS: Insulin resistance and subclinical atherosclerosis are associated with SIRT1 downregulation in monocytes. Glucotoxicity and lypotoxicity play a relevant role in quenching SIRT1 expression

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