2,300 research outputs found
The Employment Crisis and Green Orientation in Agriculture: New Educational Models
Abstract This paper will address to the subject relating to the employment emergency and will analyze which are the conditions that can foster a green shared orientation among all stakeholders in the food system. So they can help to identify ways to solve this dramatic emergency. The study will be divided into three phases: 1. desk analysis on review of current training professional profiles green oriented; 2. evaluation of green employment, labor market and the current training system, with particular reference to the gap between the needs of businesses and provision of training in the sector; 3. thoughts on new green oriented professional profiles and the necessary training. The result will provide a first assessment of the state of art concerning this fundamental condition for the development of a green society
Versos. II, Nocturnos y baladas
Copia digital. España : Ministerio de Cultura y Deporte. Subdirección General de Coordinación bibliotecaria, 2018Manuscrito autógrafo reproducido por medio de hectografÃ
Effects of Hyaluronan on Breast Cancer Aggressiveness
Simple summary: Breast cancer is the most common neoplasm in women. Although the primary tumor does not appear in a vital organ, lethality is due to the ability of tumor cells to invade and seed distant organs, causing metastases. Approaches to reduce breast cancer cell aggressiveness target hormone receptors that sustain cell growth and motility. However, other factors contribute to aberrant cell behaviors in cancer cells, and nowadays, the role of the environment surrounding cancer cells is evident. The extracellular matrix polysaccharide hyaluronan is a ubiquitous component of the tumor microenvironment that not only modulates cell growth and movement but also plays a critical role in modulating the inflammatory response. In this review, we discuss the role of hyaluronan in relation to the expression of critical hormone receptors. The expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer cells is critical for determining tumor aggressiveness and targeting therapies. The presence of such receptors allows for the use of antagonists that effectively reduce breast cancer growth and dissemination. However, the absence of such receptors in triple-negative breast cancer (TNBC) reduces the possibility of targeted therapy, making these tumors very aggressive with a poor outcome. Cancers are not solely composed of tumor cells, but also include several types of infiltrating cells, such as fibroblasts, macrophages, and other immune cells that have critical functions in regulating cancer cell behaviors. In addition to these cells, the extracellular matrix (ECM) has become an important player in many aspects of breast cancer biology, including cell growth, motility, metabolism, and chemoresistance. Hyaluronan (HA) is a key ECM component that promotes cell proliferation and migration in several malignancies. Notably, HA accumulation in the tumor stroma is a negative prognostic factor in breast cancer. HA metabolism depends on the fine balance between HA synthesis by HA synthases and degradation yielded by hyaluronidases. All the different cell types present in the tumor can release HA in the ECM, and in this review, we will describe the role of HA and HA metabolism in different breast cancer subtypes
Hyaluronan in the Cancer Cells Microenvironment
The presence of the glycosaminoglycan hyaluronan in the extracellular matrix of tissues is the result of the cooperative synthesis of several resident cells, that is, macrophages and tumor and stromal cells. Any change in hyaluronan concentration or dimension leads to a modification in stiffness and cellular response through receptors on the plasma membrane. Hyaluronan has an effect on all cancer cell behaviors, such as evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and metastasis. It is noteworthy that hyaluronan metabolism can be dramatically altered by growth factors and matrikines during inflammation, as well as by the metabolic homeostasis of cells. The regulation of HA deposition and its dimensions are pivotal for tumor progression and cancer patient prognosis. Nevertheless, because of all the factors involved, modulating hyaluronan metabolism could be tough. Several commercial drugs have already been described as potential or effective modulators; however, deeper investigations are needed to study their possible side effects. Moreover, other matrix molecules could be identified and targeted as upstream regulators of synthetic or degrading enzymes. Finally, co-cultures of cancer, fibroblasts, and immune cells could reveal potential new targets among secreted factors
Discovery of new diketopiperazines inhibiting Burkholderia cenocepacia quorum sensing in vitro and in vivo
Burkholderia cenocepacia, an opportunistic respiratory pathogen particularly relevant for cystic fibrosis patients, is difficult to eradicate due to its high level of resistance to most clinically relevant antimicrobials. Consequently, the discovery of new antimicrobials as well as molecules capable of inhibiting its virulence is mandatory. In this regard quorum sensing (QS) represents a good target for anti-virulence therapies, as it has been linked to biofilm formation and is important for the production of several virulence factors, including proteases and siderophores. Here, we report the discovery of new diketopiperazine inhibitors of the B. cenocepacia acyl homoserine lactone synthase CepI, and report their anti-virulence properties. Out of ten different compounds assayed against recombinant CepI, four were effective inhibitors, with IC50 values in the micromolar range. The best compounds interfered with protease and siderophore production, as well as with biofilm formation, and showed good in vivo activity in a Caenorhabditis elegans infection model. These molecules were also tested in human cells and showed very low toxicity. Therefore, they could be considered for in vivo combined treatments with established or novel antimicrobials, to improve the current therapeutic strategies against B. cenocepacia
Hyaluronan Produced by Smooth Muscle Cells Plays a Critical Role in Neointima Formation
Large body of evidence supports the idea that microenvironment plays a critical role in several pathologies including atherosclerosis and cancer. The amount of hyaluronan (HA) is involved in the microenvironment alterations and the concentration of this polymer reflects the progression of the diseases promoting neoangiogenesis, cell migration, and inflammation. The HA synthesis is regulated by several factors: UDP sugar precursors availability and the phosphorylation of synthetic enzyme HAS2 as well as specific drugs reducing the UDP precursors. The HAS2 phosphorylation is done by AMP kinase, a sensor of cell energy. When the cells have low energy, AMP kinase is activated and modifies covalently the regulatory enzymes, blocking all biosynthetic processes and activating the energy producing metabolism. It was recently reported that the hexosamine biosynthetic pathway (HBP) may increase the concentration of HA precursor UDP-N-acetylglucosamine (UDP-GlcNAc) leading to an increase of HA synthesis. We demonstrated that the increase of HA synthesis depends on the HAS2 post translational modification O-GlcNAcylation, which increases HA secretion modifying a residue different from the phosphorylation site of AMP kinase. In this report we highlighted the critical aspects of the post translational HAS2 regulation and its influence on HA synthesis
A case study for spacegate point-to-point transportation: Evaluation of a reference end-to-end mission operations and assessment of the associated safety aspects
The ALTEC-conducted Spacegate feasibility study addresses the opportunities offered by the sub-orbital flight with special emphasis to future generation transportation. Pursuing the same systemic methodology of the initial Spacegate definition activities, this paper focuses on some specific aspects of suborbital operations and outlines a top level end-to-end operating cycle for a reference suborbital mission spanning from pre-flight, to flight, re-entry and post landing operations and associated Ground Segment. Special focus is given to identification of suitable locations in Italy for suborbital operations, and to liftoff and re-entry phases; the results of specific simulations are also reported, showing some lift off options and the feasibility of the spiral shaped descent maneuver that improves the pilot controllability of the vehicle during the re-entry phase. Further, this paper outlines within the selected reference mission, the main safety aspects considered as driving factors in planning and implementing future generation transportation; areas such as launch/landing range and relevant risk management/mitigation policies, as well as selection of safety driving criteria in the definition of trajectories and space transition corridors, and capabilities to monitor the vehicle ascent and re-entry will be assessed. Safety regulations will also be evaluated to protect launch range, drive spaceport site selection and consequently the ability of the spaceport to accommodate large numbers of passengers and participants, as well as a number of simultaneous operations such as training, vehicle integration tasks, and passenger preparation for flight. For human flight in general, and in particular for commercial point to point activities at this early stage, it is vital to minimize risk since a fatal accident at the very beginning of flights will put the entire business in jeopardy. The regulatory challenges with regards to safety will also be outlined in this paper, related to executing Spacegate activities in Europe and collaborations with the involved Agencies in the USA and Europe (FAA, ENAC, ENAV, SESAR, EASA) will be explored; in particular, some initiatives have already been started, that include active ALTEC participation to the IAASS Space Safety Technical Committee (SSTC) that was created to contribute to the advancement of the Safety in the area of the "Commercial Suborbital Flight"
Short-term complexity of cardiac autonomic control during sleep: REM as a potential risk factor for cardiovascular system in aging.
peer reviewedINTRODUCTION: Sleep is a complex phenomenon characterized by important modifications throughout life and by changes of autonomic cardiovascular control. Aging is associated with a reduction of the overall heart rate variability (HRV) and a decrease of complexity of autonomic cardiac regulation. The aim of our study was to evaluate the HRV complexity using two entropy-derived measures, Shannon Entropy (SE) and Corrected Conditional Entropy (CCE), during sleep in young and older subjects. METHODS: A polysomnographic study was performed in 12 healthy young (21.1+/-0.8 years) and 12 healthy older subjects (64.9+/-1.9 years). After the sleep scoring, heart period time series were divided into wake (W), Stage 1-2 (S1-2), Stage 3-4 (S3-4) and REM. Two complexity indexes were assessed: SE(3) measuring the complexity of a distribution of 3-beat patterns (SE(3) is higher when all the patterns are identically distributed and it is lower when some patterns are more likely) and CCE(min) measuring the minimum amount of information that cannot be derived from the knowledge of previous values. RESULTS: Across the different sleep stages, young subjects had similar RR interval, total variance, SE(3) and CCE(min). In the older group, SE(3) and CCE(min) were reduced during REM sleep compared to S1-2, S3-4 and W. Compared to young subjects, during W and sleep the older subjects showed a lower RR interval and reduced total variance as well as a significant reduction of SE(3) and CCE(min). This decrease of entropy measures was more evident during REM sleep. CONCLUSION: Our study indicates that aging is characterized by a reduction of entropy indices of cardiovascular variability during wake/sleep cycle, more evident during REM sleep. We conclude that during aging REM sleep is associated with a simplification of cardiac control mechanisms that could lead to an impaired ability of the cardiovascular system to react to cardiovascular adverse events
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