Influence of storage environment on maize grain: CO2 production, dry matter losses and aflatoxins contamination

Poor storage of cereals, such as maize can lead to both nutritional losses and mycotoxin contamination. The aim of this study was to examine the respiration of maize either naturally contaminated or inoculated with Aspergillus flavus to examine whether this might be an early and sensitive indicator of aflatoxin (AF) contamination and relative storability risk. We thus examined the relationship between different interacting storage environmental conditions (0.80–0.99 water activity (aw) and 15–35°C) in naturally contaminated and irradiated maize grain + A. flavus on relative respiration rates (R), dry matter losses (DMLs) and aflatoxin B1 and B2 (AFB1-B2) contamination. Temporal respiration and total CO2 production were analysed by GC-TCD, and results used to calculate the DMLs due to colonisation. AFs contamination was quantified at the end of the storage period by HPLC MS/MS. The highest respiration rates occurred at 0.95 aw and 30–35°C representing between 0.5% and 18% DMLs. Optimum AFs contamination was at the same aw at 30°C. Highest AFs contamination occurred in maize colonised only by A. flavus. A significant positive correlation between % DMLs and AFB1 contamination was obtained (r = 0.866, p < 0.001) in the irradiated maize treatments inoculated with A. flavus. In naturally contaminated maize + A. flavus inoculum loss of only 0.56% DML resulted in AFB1 contamination levels exceeding the EU legislative limits for food. This suggests that there is a very low threshold tolerance during storage of maize to minimise AFB1 contamination. This data can be used to develop models that can be effectively used in enhancing management for storage of maize to minimise risks of mycotoxin contamination

VKORC1 mutation in European populations of Rattus norvegicus with first data for Italy and the report of a new amino acid substitution.

In the Norway rat, Rattus norvegicus, anticoagulant rodenticide resistance is mainly associated with mutations in the third exon of the Vitamin K epoxide reductase complex subunit 1 (VKORC1). Identification of the resistant wild populations is very important to improve the control practices and to limit the damages due to inadequate use of the anticoagulant rodenticide. In this study, we determined the distribution of the third exon mutations in poorly investigated areas of Africa, Europe and the Middle East. In particular, we investigated the phenomenon for the first time in the Italian peninsula. We obtained sequences of the third exon for 133 Norway rats from 37 localities in Africa, Europe and the Middle East. For additional analysis, we retrieved information in literature on amino acid substitution in 1136 third exon sequences of Norway rats from Europe, the Far East, North America and South America. However, we found third exon mutations only in Europe and the Far East with the Y139F mutation shared between the two areas. Europe has the higher number of mutant individuals and Y139C mutation prevails. In Italy, we found a single missense mutation (I123S) in a Venetian locality. This homozygote mutation, is not know in literature to be associated with resistance, but it is very similar to a mutation that confers resistance in humans (I123N). This similarity and its high local frequency makes it a good candidate for future testing. Our results provide useful data to better understand the resistance phenomenon and to plan targeted control actions

Modulation of presynaptic plasticity and learning by the H-ras/extracellular signal-regulated kinase/synapsin I signaling pathway

Molecular and cellular studies of the mechanisms underlying mammalian learning and memory have focused almost exclusively on postsynaptic function. We now reveal an experience-dependent presynaptic mechanism that modulates learning and synaptic plasticity in mice. Consistent with a presynapticfunctionfor endogenous H-ras/extracellular signal-regulated kinase (ERK) signaling, we observed that, under normal physiologic conditions in wild-type mice, hippocampus-dependent learning stimulated the ERK-dependent phosphorylation of synapsin I, and MEK (MAP kinase kinase)/ERK inhibition selectively decreased the frequency of miniature EPSCs. By generating transgenic mice expressing a constitutively active form of H-ras (H-rasG12V), which is abundantly localized in axon terminals, we were able to increase the ERK-dependent phosphorylation of synapsin I. This resulted in several presynaptic changes, including a higher density of docked neurotransmitter vesiclesin glutamatergicterminals, anincreasedfrequency of miniature EPSCs, andincreased paired-pulse facilitation. In addition, we observed facilitated neurotransmitter release selectively during high-frequency activity with consequent increases in long-term potentiation. Moreover, these mice showed dramatic enhancements in hippocampus-dependent learning. Importantly, deletion of synapsin I, an exclusively presynaptic protein, blocked the enhancements of learning, presynaptic plasticity, and long-term potentiation. Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory

Application of life cycle thinking towards sustainable cities : a review

Unidad de excelencia María de Maeztu MdM-2015-0552Defining sustainable cities is not straightforward. The main issues involved in urban sustainability are buildings, energy, food, green areas and landscape, mobility, urban planning, water and waste; and their improvement is promoted through different strategies. However, a quantitative method, such as life cycle thinking (LCT), is essential to evaluating these strategies. This paper reviews LCT studies related to urban issues to identify the main research gaps in the evaluation of these improvement strategies. The review identifies the main sustainability strategies associated with each urban issue and compiles articles that deal with these strategies through LCT, including environmental life cycle assessment (LCA), life cycle costing (LCC), social LCA (S-LCA) and life cycle sustainability assessment (LCSA), as well as integrated analyses with combined tools. Water, waste and buildings are the urban issues that accounted for a larger amount of studies. In contrast, a limited number of papers assessed urban planning and energy (excluding energy in buildings). Strong interrelations among urban issues were identified, most of them including water. In terms of methods, 79% of the studies exclusively applied life cycle tools (i.e., LCA, LCC, S-LCA or LCSA). Within this group, the environmental dimension was the focus of 84% of the papers. Single environmental indicators (e.g., global warming) were common in 20% of the analyses, highlighting the need to integrate more impact categories to prevent trade-offs. In the field of social and sustainability assessment, there is a need for methodological advances that foster their application in urban areas. Further research should cover the thematic and methodological gaps identified in this paper, such as developing models that assess complex urban issues, generating comprehensive LCT studies and promoting multi-indicators. Life cycle tools might benefit from revising the methodology with stakeholders to optimize the understanding and communication of life cycle results for policy- and decision-making processes

Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients

Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets

Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response

Simple Summary Triple-negative breast cancer (TNBC) is currently in the clinical research spotlight because of the tumor's aggressive and invasive nature and the scarcity of therapeutic targets. Despite recent advances in identifying reliable prognostic biomarkers in the tumor microenvironment (TME), rigorous evaluation of their predictive capacity remains challenging. We describe the immune cellular and genetic profile of the residual tumor of TNBC that does not achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). A high concentration of lymphocytes and dendritic cells, as well as genetic TME markers such as MUC-1 and CXCL13 in the residual tumor, are valuable prognostic factors of survival and relapse in TNBC patients. From a clinical health perspective, a thorough understanding of the composition of the TME and its prognostic implications might yield relevant immunological information and reveal key predictive biomarkers. This could ultimately help substantially improve the outcomes of residual cancer-burdened TNBC patients after NAC. With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan-Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling

VKORC1 mutation in European populations of Rattus norvegicus with first data for Italy and the report of a new amino acidic substitution

In the Norway rat, Rattus norvegicus, anticoagulant rodenticide resistance is mainly associated with mutations in the third exon of the Vitamin K epoxide reductase complex subunit 1 (VKORC1). Identification of the resistant wild populations is very important to improve the control practices and to limit the damages due to inadequate use of the anticoagulant rodenticide. In this study, we determined the distribution of the third exon mutations in poorly investigated areas of Africa, Europe and the Middle East. In particular, we investigated the phenomenon for the first time in the Italian peninsula. We obtained sequences of the third exon for 133 Norway rats from 37 localities in Africa, Europe and the Middle East. For additional analysis, we retrieved information in literature on amino acid substitution in 1136 third exon sequences of Norway rats from Europe, the Far East, North America and South America. However, we found third exon mutations only in Europe and the Far East with the Y139F mutation shared between the two areas. Europe has the higher number of mutant individuals and Y139C mutation prevails. In Italy, we found a single missense mutation (I123S) in a Venetian locality. This homozygote mutation, is not know in literature to be associated with resistance, but it is very similar to a mutation that confers resistance in humans (I123N). This similarity and its high local frequency makes it a good candidate for future testing. Our results provide useful data to better understand the resistance phenomenon and to plan targeted control actions

PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study

<p>Abstract</p> <p>Background</p> <p>The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality.</p> <p>Methods</p> <p>In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor.</p> <p>Results</p> <p>Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009).</p> <p>Conclusion</p> <p>Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients.</p

The second ACTRIS inter-comparison (2016) for Aerosol Chemical Speciation Monitors (ACSM) : Calibration protocols and instrument performance evaluations

AbstractThis work describes results obtained from the 2016 Aerosol Chemical Speciation Monitor (ACSM) intercomparison exercise performed at the Aerosol Chemical Monitor Calibration Center (ACMCC, France). Fifteen quadrupole ACSMs (Q_ACSM) from the European Research Infrastructure for the observation of Aerosols, Clouds and Trace gases (ACTRIS) network were calibrated using a new procedure that acquires calibration data under the same operating conditions as those used during sampling and hence gets information representative of instrument performance. The new calibration procedure notably resulted in a decrease in the spread of the measured sulfate mass concentrations, improving the reproducibility of inorganic species measurements between ACSMs as well as the consistency with co-located independent instruments. Tested calibration procedures also allowed for the investigation of artifacts in individual instruments, such as the overestimation of m/z 44 from organic aerosol. This effect was quantified by the m/z (mass-to-charge) 44 to nitrate ratio measured during ammonium nitrate calibrations, with values ranging from 0.03 to 0.26, showing that it can be significant for some instruments. The fragmentation table correction previously proposed to account for this artifact was applied to the measurements acquired during this study. For some instruments (those with high artifacts), this fragmentation table adjustment led to an ?overcorrection? of the f44 (m/z 44/Org) signal. This correction based on measurements made with pure NH4NO3, assumes that the magnitude of the artifact is independent of chemical composition. Using data acquired at different NH4NO3 mixing ratios (from solutions of NH4NO3 and (NH4)2SO4) we observe that the magnitude of the artifact varies as a function of composition. Here we applied an updated correction, dependent on the ambient NO3 mass fraction, which resulted in an improved agreement in organic signal among instruments. This work illustrates the benefits of integrating new calibration procedures and artifact corrections, but also highlights the benefits of these intercomparison exercises to continue to improve our knowledge of how these instruments operate, and assist us in interpreting atmospheric chemistry.Peer reviewe

ACTRIS ACSM intercomparison – Part 1: Reproducibility of concentration and fragment results from 13 individual Quadrupole Aerosol Chemical Speciation Monitors (Q-ACSM) and consistency with co-located instruments

As part of the European ACTRIS project, the first large Quadrupole Aerosol Chemical Speciation Monitor (Q-ACSM) intercomparison study was conducted in the region of Paris for 3 weeks during the late-fall – early-winter period (November–December 2013). The first week was dedicated to the tuning and calibration of each instrument, whereas the second and third were dedicated to side-by-side comparison in ambient conditions with co-located instruments providing independent information on submicron aerosol optical, physical, and chemical properties. Near real-time measurements of the major chemical species (organic matter, sulfate, nitrate, ammonium, and chloride) in the non-refractory submicron aerosols (NR-PM1) were obtained here from 13 Q-ACSM. The results show that these instruments can produce highly comparable and robust measurements of the NR-PM1 total mass and its major components. Taking the median of the 13 Q-ACSM as a reference for this study, strong correlations (r2 > 0.9) were observed systematically for each individual Q-ACSM across all chemical families except for chloride for which three Q-ACSMs showing weak correlations partly due to the very low concentrations during the study. Reproducibility expanded uncertainties of Q-ACSM concentration measurements were determined using appropriate methodologies defined by the International Standard Organization (ISO 17025, 1999) and were found to be 9, 15, 19, 28, and 36 % for NR-PM1, nitrate, organic matter, sulfate, and ammonium, respectively. However, discrepancies were observed in the relative concentrations of the constituent mass fragments for each chemical component. In particular, significant differences were observed for the organic fragment at mass-to-charge ratio 44, which is a key parameter describing the oxidation state of organic aerosol. Following this first major intercomparison exercise of a large number of Q-ACSMs, detailed intercomparison results are presented, along with a discussion of some recommendations about best calibration practices, standardized data processing, and data treatment.JRC.H.2-Air and Climat