Segmented Bayesian calibration approach for estimating age in forensic science

Forensic age estimation is receiving growing attention from researchers in the last few years. Accurate estimates of age are needed both for identifying real age in individuals without any identity document and assessing it for human remains. The methods applied in such context are mostly based on radiological analysis of some anatomical districts and entail the use of a regression model. However, estimating chronological age by regression models leads to overestimated ages in younger subjects and underestimated ages in older ones. We introduced a full Bayesian calibration method combined with a segmented function for age estimation that relied on a Normal distribution as a density model to mitigate this bias. In this way, we were also able to model the decreasing growth rate in juveniles. We compared our new Bayesian‐segmented model with other existing approaches. The proposed method helped producing more robust and precise forecasts of age than compared models while exhibited comparable accuracy in terms of forecasting measures. Our method seemed to overcome the estimation bias also when applied to a real data set of South‐African juvenile subjects.     

Taurine supplementation in conjunction with exercise modulated cytokines and improved subcutaneous white adipose tissue plasticity in obese women

Amino Acids - Interventions that can modulate subcutaneous white adipose tissue (scWAT) function, such as exercise training and nutritional components, like taurine, modulate the inflammatory...     

Older rhesus macaque infants are more susceptible to oral infection with simian-human immunodeficiency virus 89.6P than neonates

Earlier primate studies revealed that oral transmission of immunodeficiency viruses can occur at all ages [R. M. Ruprecht et al., J. Infect. Dis. 179(Suppl. 3):S408-S412, 1999]. Using a stock of pathogenic simian-human immunodeficiency virus, SHIV89.6P, we compared the 50% animal infectious dose needed to achieve systemic infection after oral challenge in newborn and older infant or juvenile rhesus macaques. Unexpectedly, the older monkeys required a 150-fold-lower virus challenge dose than the neonates (P=3.3 x 10(-5)). In addition, at least 60,000 times more virus was needed to achieve systemic infection in neonates by the oral route than by the intravenous route (P <1 x 10(-5)). Thus, route of inoculation and age are important determinants of SHIV89.6P infectivity in rhesus macaques.     

A reappraisal of the central effects of botulinum neurotoxin type A: by what mechanism?

Botulinum neurotoxin A (BoNT/A) is a metalloprotease that enters peripheral motor nerve terminals and blocks the release of acetylcholine via the specific cleavage of the synaptosomal-associated protein of 25-kDa. Localized injections of BoNT/A are widely employed in clinical neurology to treat several human diseases characterized by muscle hyperactivity. It is generally assumed that the effects of BoNT/A remain localized to the injection site. However, several neurophysiological studies have provided evidence for central effects of BoNT/A, raising the issue of how these actions arise. Here we review these data and discuss the possibility that retrograde axonal transport of catalytically active BoNT/A may explain at least some of its effects at the level of central circuits.     

p38 MAPK downregulates phosphorylation of Bad in doxorubicin-induced endothelial apoptosis

Doxorubicin is the anthracycline with the widest spectrum of antitumor activity, and it has been shown that the antitumor activity is mediated in vivo by selective triggering of apoptosis in proliferating endothelial cells. We studied cultured human endothelial cells and observed that doxorubicin-induced apoptosis was mediated by p38 mitogen-activated protein kinase (MAPK). Doxorubicin-provoked apoptosis was significantly inhibited by expression of dominant negative p38 MAPK or pharmacological inhibition with SB203580. Furthermore, blocking phosphatidylinositol-3-kinase/Akt signaling significantly increased doxorubicin-induced caspase-3 activity and cell death, indicating that Akt is a survival factor in this system. Notably, we also found that doxorubicin-provoked apoptosis included p38 MAPK-mediated inhibition of Akt and Bad phosphorylation. Furthermore, doxorubicin-stimulated phosphorylation of Bad in cells expressing dominant negative p38 MAPK was impeded by the inhibition of PI3-K. In addition to the impact on Bad phosphorylation, doxorubicin-treatment caused p38 MAPK-dependent downregulation of Bcl-xL protein.     

Ago1 and Ago2 differentially affect cell proliferation, motility and apoptosis when overexpressed in SH-SY5Y neuroblastoma cells

Argonaute are a conserved class of proteins central to the microRNA pathway. We have highlighted a novel and non-redundant function of Ago1 versus Ago2; the two core factors of the miRNA-associated RISC complex. Stable overexpression of Ago1 in neuroblastoma cells causes the cell cycle to slow down, a decrease in cellular motility and a stronger apoptotic response upon UV irradiation. These effects, together with a significant increase in p53 levels, suggest that Ago1 may act as a tumor-suppressor factor, a function also supported by GEO Profiles microarrays that inversely correlate Ago1 expression levels with cell proliferation rates.     

Uptake kinetics of different arsenic species by Brassica carinata

The time- and concentration-dependent uptake kinetics for arsenate and arsenite were determined in 15-day-old excised roots. In both cases, arsenite showed a mono-phasic influx with the isotherm data fitting a linear model better than a non-linear one. The time- and the concentration-dependent uptake of arsenate displayed a hyperbolic kinetic. Greater uptake of arsenate, compared with arsenite, was found especially at lower external substrate concentrations. Competitive inhibition of uptake with phosphate showed that arsenite and arsenate were taken up by different uptake systems because arsenate uptake was strongly inhibited in the presence of phosphate, whereas arsenite uptake was not affected.     

Surveillance of the chikungunya vector Aedes albopictus (Skuse) in Emilia‐Romagna (northern Italy): organizational and technical aspects of a large scale monitoring system

The chikungunya virus outbreak that occurred in 2007 in northern Italy (Emilia‐Romagna region) prompted the development of a large scale monitoring system of the population density of Aedes albopictus (Skuse, 1894), comparable at the provincial and municipal levels. In 2007, egg density data presented an aggregated distribution (VMR >1) and Taylor's power law was applied to calculate the minimum number of ovitraps needed to obtain the prefixed precision levels: D=0.2 in the areas where the chikungunya epidemic occurred and D=0.3 in all the other urban areas >600 ha. The estimated minimum ovitrap number was then used to set up a monitoring network at the regional scale in season 2008 (May‐October). In 242 municipalities 2,741 ovitraps were activated and the 2008 sampled data showed a similar aggregated distribution as in 2007. The adequacy of the monitoring design was evaluated by recalculating the Taylor's coefficients and the minimum ovitrap number for each urban area >600 ha using the 2008 egg density data. The comparison between the two estimates showed that the minimum ovitrap number calculated in 2007 was underestimated by 2.7% in weeks 22–41 but was overestimated by 29.4% if referring to the period of highest population density (weeks 27–37). The low cost of the proposed monitoring system, based on the use of fortnightly checked ovitraps, could make it economically sustainable even in a non‐epidemic season.     

Leishmania inhibitor of serine peptidase 2 prevents TLR4 activation by neutrophil elastase promoting parasite survival in murine macrophages

Leishmania major is a protozoan parasite that causes skin ulcerations in cutaneous leishmaniasis. In the mammalian host, the parasite resides in professional phagocytes and has evolved to avoid killing by macrophages. We identified L. major genes encoding inhibitors of serine peptidases (ISPs), which are orthologs of bacterial ecotins, and found that ISP2 inhibits trypsin-fold S1A family peptidases. In this study, we show that L. major mutants deficient in ISP2 and ISP3 (Δisp2/3) trigger higher phagocytosis by macrophages through a combined action of the complement type 3 receptor, TLR4, and unregulated activity of neutrophil elastase (NE), leading to parasite killing. Whereas all three components are required to mediate enhanced parasite uptake, only TLR4 and NE are necessary to promote parasite killing postinfection. We found that the production of superoxide by macrophages in the absence of ISP2 is the main mechanism controlling the intracellular infection. Furthermore, we show that NE modulates macrophage infection in vivo, and that the lack of ISP leads to reduced parasite burdens at later stages of the infection. Our findings support the hypothesis that ISPs function to prevent the activation of TLR4 by NE during the Leishmania-macrophage interaction to promote parasite survival and growth.