Intelligent Transport Systems: how to Manage a Research in a new Field in IS

This paper sheds light on the management of a research project in a new topic for IS like the one of Intelligent Transport Systems (ITS). It describes and discusses the methodology adopted for a survey designed by the authors and experimented during a recent research on ITS carried out on behalf of an Italian Ministry. The paper presents the first results of this research and draw some conclusions on the problems that have to be faced in order to successfully manage such type of research projects and to build a common knowledge base on ITS.This paper sheds light on the management of a research project in a new topic for IS like the one of Intelligent Transport Systems (ITS). It describes and discusses the methodology adopted for a survey designed by the authors and experimented during a recent research on ITS carried out on behalf of an Italian Ministry. The paper presents the first results of this research and draw some conclusions on the problems that have to be faced in order to successfully manage such type of research projects and to build a common knowledge base on ITS.Monograph's chapter

Brown rice and pulses for the development of shelf-stable and low glycemic index ready-to-eat meals

Shelf-stable low glycemic index ready-to-eat (RTE) risotto meals (in pouches) containing brown rice and pulses (recipe A = chickpeas; recipe B = lentils, and beans) were developed, stored for 12-months at room temperature, and characterized over time. RTE meals were heated in microwave (replicating home consumption procedure), and analyzed for in vitro starch digestibility, textural attributes, and consumer acceptability. Digestible starch fractions were similar in the formulations during storage, and in vivo testing demonstrated low glycemic indexes (recipe A = 43.5 ± 6.8; recipe B = 31.8 ± 6.5) for the two meals. Hardness of risotto components increased during storage and microwave heating did not fully recover textural attibutes characteristic of the fresh product. Consumers’ (50) acceptability remained high (>5.5 out of 9) until the end of storage. This study demonstrates brown rice with pulses can be used for developing stable and accepted ready-to-eat meals having low glycemic indexes

Optical modulation of excitation-contraction coupling in human-induced pluripotent stem cell-derived cardiomyocytes

Non-genetic photostimulation is a novel and rapidly growing multidisciplinary field that aims to induce light-sensitivity in living systems by exploiting exogeneous phototransducers. Here, we propose an intramembrane photoswitch, based on an azobenzene derivative (Ziapin2), for optical pacing of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The light-mediated stimulation process has been studied by applying several techniques to detect the effect on the cell properties. In particular, we recorded changes in membrane capacitance, in membrane potential (V-m), andmodulation of intracellular Ca2+ dynamics. Finally, cell contractility was analyzed using a custom MATLAB algorithm. Photostimulation of intramembrane Ziapin2 causes a transient V-m hyperpolarization followed by a delayed depolarization and action potential firing. The observed initial electrical modulation nicely correlates with changes in Ca2+ dynamics and contraction rate. This work represents the proof of principle that Ziapin2 can modulate electrical activity and contractility in hiPSC-CMs, opening up a future development in cardiac physiology

Clinical trial units and clinical research coordinators: a system facing crisis?

We are currently witnessing an increase in procedural and managerial complexities within the field of clinical research, which require greater human and infrastructural resources as well as imply the need for a greater skill set and expertise on the part of professionals. Within this frame of reference clinical trial units and clinical research coordinators play a vital role in the design and conduct of clinical trials in Italy. There is a current recruitment and retention crisis for this specialist role due to a complex set of factors, most likely to have come to a head due to the lack of recognition at the Italian institutional level, that lead to precarious work contracts, lack of identity, and excessive turnover at experimental sites. This article, led by the Italian Group of Clinical Research Coordinator (GIDMcrc), presents some of the issues and ways in which national stakeholders may be able to address this

Nuclear Shield: A Multi-Enzyme Task-Force for Nucleus Protection

In eukaryotic cells the nuclear envelope isolates and protects DNA from molecules that could damage its structure or interfere with its processing. Moreover, selected protection enzymes and vitamins act as efficient guardians against toxic compounds both in the nucleoplasm and in the cytosol. The observation that a cytosolic detoxifying and antioxidant enzyme i.e. glutathione transferase is accumulated in the perinuclear region of the rat hepatocytes suggests that other unrecognized modalities of nuclear protection may exist. Here we show evidence for the existence of a safeguard enzyme machinery formed by an hyper-crowding of cationic enzymes and proteins encompassing the nuclear membrane and promoted by electrostatic interactions

The absence of abdominal pigmentation in livestock associated culicoides following artificial blood feeding and the epidemiological implication for arbovirus surveillance

Culicoides midges (Diptera: Ceratopogonidae), the vectors of economically important arboviruses such as bluetongue virus and African horse sickness virus, are of global importance. In the absence of transovarial transmission, the parity rate of a Culicoides population provides imperative information regarding the risk of virus dispersal. Abdominal pigmentation, which develops after blood feeding and ovipositioning, is used as an indicator of parity in Culicoides. During oral susceptibility trials over the last three decades, a persistent proportion of blood engorged females did not develop pigment after incubation. The present study, combining a number of feeding trials and different artificial feeding methods, reports on this phenomenon, as observed in various South African and Italian Culicoides species and populations. The absence of pigmentation in artificial blood-fed females was found in at least 23 Culicoides species, including important vectors such as C. imicola, C. bolitinos, C. obsoletus, and C. scoticus. Viruses were repeatedly detected in these unpigmented females after incubation. Blood meal size seems to play a role and this phenomenon could be present in the field and requires consideration, especially regarding the detection of virus in apparent “nulliparous” females and the identification of overwintering mechanisms and seasonally free vector zones.This publication is part of the project “ArtOmic” (Grant number RF-2016-02362851) which has received funding from the Italian Ministry of Health’s Ricerca Finalizzata programme (2016).https://www.mdpi.com/journal/pathogensam2022Veterinary Tropical Disease

Macrophage polarization and metabolism in atherosclerosis

: Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of fatty deposits in the inner walls of vessels. these plaques restrict blood flow and lead to complications such as heart attack or stroke. the development of atherosclerosis is influenced by a variety of factors, including age, genetics, lifestyle, and underlying health conditions such as high blood pressure or diabetes. atherosclerotic plaques in stable form are characterized by slow growth, which leads to luminal stenosis, with low embolic potential or in unstable form, which contributes to high risk for thrombotic and embolic complications with rapid clinical onset. In this complex scenario of atherosclerosis, macrophages participate in the whole process, including the initiation, growth and eventually rupture and wound healing stages of artery plaque formation. macrophages in plaques exhibit high heterogeneity and plasticity, which affect the evolving plaque microenvironment, e.g., leading to excessive lipid accumulation, cytokine hyperactivation, hypoxia, apoptosis and necroptosis. the metabolic and functional transitions of plaque macrophages in response to plaque microenvironmental factors not only influence ongoing and imminent inflammatory responses within the lesions but also directly dictate atherosclerotic progression or regression. In this review, we discuss the origin of macrophages within plaques, their phenotypic diversity, metabolic shifts, and fate and the roles they play in the dynamic progression of atherosclerosis. It also describes how macrophages interact with other plaque cells, particularly T cells. ultimately, targeting pathways involved in macrophage polarization may lead to innovative and promising approaches for precision medicine. further insights into the landscape and biological features of macrophages within atherosclerotic plaques may offer valuable information for optimizing future clinical treatment for atherosclerosis by targeting macrophages

IL-21 is a major negative regulator of IRF4-dependent lipolysis affecting Tregs in adipose tissue and systemic insulin sensitivity.

Obesity elicits immune cell infiltration of adipose tissue provoking chronic low-grade inflammation. Regulatory T cells (Tregs) are specifically reduced in adipose tissue of obese animals. Since interleukin (IL)-21 plays an important role in inducing and maintaining immune-mediated chronic inflammatory processes and negatively regulates Treg differentiation/activity, we hypothesized that it could play a role in obesity-induced insulin resistance. We found IL-21 and IL-21R mRNA expression upregulated in adipose tissue of high-fat diet (HFD) wild-type (WT) mice and in stromal vascular fraction from human obese subjects in parallel to macrophage and inflammatory markers. Interestingly, a larger infiltration of Treg cells was seen in the adipose tissue of IL-21 knockout (KO) mice compared with WT animals fed both normal diet and HFD. In a context of diet-induced obesity, IL-21 KO mice, compared with WT animals, exhibited lower body weight, improved insulin sensitivity, and decreased adipose and hepatic inflammation. This metabolic phenotype is accompanied by a higher induction of interferon regulatory factor 4 (IRF4), a transcriptional regulator of fasting lipolysis in adipose tissue. Our data suggest that IL-21 exerts negative regulation on IRF4 and Treg activity, developing and maintaining adipose tissue inflammation in the obesity state

Interface Gain-of-Function Mutations in TLR7 Cause Systemic and Neuro-inflammatory Disease

TLR7 recognizes pathogen-derived single-stranded RNA (ssRNA), a function integral to the innate immune response to viral infection. Notably, TLR7 can also recognize self-derived ssRNA, with gain-of-function mutations in human TLR7 recently identified to cause both early-onset systemic lupus erythematosus (SLE) and neuromyelitis optica. Here, we describe two novel mutations in TLR7, F507S and L528I. While the L528I substitution arose de novo, the F507S mutation was present in three individuals from the same family, including a severely affected male, notably given that the TLR7 gene is situated on the X chromosome and that all other cases so far described have been female. The observation of mutations at residues 507 and 528 of TLR7 indicates the importance of the TLR7 dimerization interface in maintaining immune homeostasis, where we predict that altered homo-dimerization enhances TLR7 signaling. Finally, while mutations in TLR7 can result in SLE-like disease, our data suggest a broader phenotypic spectrum associated with TLR7 gain-of-function, including significant neurological involvement

Antagomir-17-5p Abolishes the Growth of Therapy-Resistant Neuroblastoma through p21 and BIM

We identified a key oncogenic pathway underlying neuroblastoma progression: specifically, MYCN, expressed at elevated level, transactivates the miRNA 17-5p-92 cluster, which inhibits p21 and BIM translation by interaction with their mRNA 3′ UTRs. Overexpression of miRNA 17-5p-92 cluster in MYCN-not-amplified neuroblastoma cells strongly augments their in vitro and in vivo tumorigenesis. In vitro or in vivo treatment with antagomir-17-5p abolishes the growth of MYCN-amplified and therapy-resistant neuroblastoma through p21 and BIM upmodulation, leading to cell cycling blockade and activation of apoptosis, respectively. In primary neuroblastoma, the majority of cases show a rise of miR-17-5p level leading to p21 downmodulation, which is particularly severe in patients with MYCN amplification and poor prognosis. Altogether, our studies demonstrate for the first time that antagomir treatment can abolish tumor growth in vivo, specifically in therapy-resistant neuroblastoma