cis-acting sequences and trans-acting factors in the localization of mRNA for mitochondrial ribosomal proteins

mRNA localization is a conserved post-transcriptional process crucial for a variety of systems. Although several mechanisms have been identified, emerging evidence suggests that most transcripts reach the protein functional site by moving along cytoskeleton elements. We demonstrated previously that mRNA for mitochondrial ribosomal proteins are asymmetrically distributed in the cytoplasm, and that localization in the proximity of mitochondria is mediated by the 3′-UTR. Here we show by biochemical analysis that these mRNA transcripts are associated with the cytoskeleton through the microtubule network. Cytoskeleton association is functional for their intracellular localization near the mitochondrion, and the 3′-UTR is involved in this cytoskeleton-dependent localization. To identify the minimal elements required for localization, we generated DNA constructs containing, downstream from the GFP gene, deletion mutants of mitochondrial ribosomal protein S12 3′-UTR, and expressed them in HeLa cells. RT-PCR analysis showed that the localization signals responsible for mRNA localization are located in the first 154 nucleotides. RNA pulldown assays, mass spectrometry, and RNP immunoprecipitation assay experiments, demonstrated that mitochondrial ribosomal protein S12 3′-UTR interacts specifically with TRAP1 (tumor necrosis factor receptor-associated protein1), hnRNPM4 (heterogeneous nuclear ribonucleoprotein M4), Hsp70 and Hsp60 (heat shock proteins 70 and 60), and α-tubulin in vitro and in vivo

A REVIEW OF THE PUBLIC HEALTH AND MENTAL HEALTH ROLES IN RESPONSE TO COMMUNITY DISASTERS AND THE RATIONALE FOR EFFECTIVE INTERDISCIPLINARY COLLABORATIONS

Disasters vary in scope, size, and cause. Relevant public health aspects of disasters include community impact and the response of health professionals to alleviate stress and dangerous conditions surrounding the disaster. Public health focuses on the prevention of disease and the promotion of health. Disaster preparedness and response are significant areas in the field of public health. Disasters pose threats to the general public through increases in injury, death, and changes in infrastructure. The public health response to disaster includes assessments of the community impact, surveillance for disease, addressing sanitary health concerns, and providing information to the public. Mental health professionals also have important roles in responding to disaster in the community. In addition to physical aspects, disasters also may pose psychological risks to individuals and to the effected community. These risks may include stress, anxiety, and depression. Mental health workers provide counseling, support, and education to assist people affected by disaster in returning to their pre-disaster level of functioning. Traditionally there has been a separation between the disciplines of public health and mental health. Public health is population-based and mental health has been traditionally regarded being more individually based. During a disastrous event communication and organization among agencies is critical to an effective response. Increased collaborations between public health and mental health are needed to facilitate an appropriate and effective disaster response. Both areas aim to improve overall health and well being, and therefore are inter-related. Each discipline needs to become more familiar with the nature of each other's work. Overall increases in public and mental health research, planning, training, and education programs are needed to understand and appreciate both the public health and mental health consequences of disaster and to improve community participation and preparedness

Our products are safe (don't tell anyone!). Why don't supermarkets advertise their private food safety standards?

Large retail chains have spent considerable resources to promote production protocols and traceability across the supply chain, aiming at increasing food safety. Yet, the majority of consumers are unaware of these private food safety standards (PFSS) and retailers are not informing them. This behavior denotes a pooling paradox: supermarkets spend a large amount of money for food safety and yet they forget to inform consumers. The result is a pooling equilibrium where consumers cannot discriminate among high quality and low quality products and supermarkets give up the potential price premium. This paper provides an economic explanation for the paradox using a contract-theory model. We found that PFSS implementation may be rational even if consumers have no willingness to pay for safety, because the standard can be used as a tool to solve asymmetric information along the supply chain. Using the PFSS, supermarkets can achieve a separating equilibrium where opportunistic suppliers have no incentive to accept the contract. Even if consumers exhibit a limited (but strictly positive) willingness to pay for safety, advertising may be profit-reducing. If the expected price margin is high enough, supermarkets have incentive to supply both certified and uncertified products. In this case, we show that, if consumers perceive undifferentiated products as “reasonably safe”, supermarkets may maximize profits by pooling the goods and selling them as undifferentiated. This result is not driven by advertising costs, as we derive it assuming free advertising.Agribusiness, Food Consumption/Nutrition/Food Safety,

RISK ASSESSMENT OF MALICIOUS ATTACKS AGAINST POWER SYSTEMS

The new scenarios of malicious attack prompt for their deeper consideration and mainly when critical systems are at stake. In this framework, infrastructural systems, including power systems, represent a possible target due to the huge impact they can have on society. Malicious attacks are different in their nature from other more traditional cause of threats to power system, since they embed a strategic interaction between the attacker and the defender (characteristics that cannot be found in natural events or systemic failures). This difference has not been systematically analyzed by the existent literature. In this respect, new approaches and tools are needed. This paper presents a mixed-strategy game-theory model able to capture the strategic interactions between malicious agents that may be willing to attack power systems and the system operators, with its related bodies, that are in charge of defending them. At the game equilibrium, the different strategies of the two players, in terms of attacking/protecting the critical elements of the systems, can be obtained. The information about the attack probability to various elements can be used to assess the risk associated with each of them, and the efficiency of defense resource allocation is evidenced in terms of the corresponding risk. Reference defense plans related to the online defense action and the defense action with a time delay can be obtained according to their respective various time constraints. Moreover, risk sensitivity to the defense/attack-resource variation is also analyzed. The model is applied to a standard IEEE RTS-96 test system for illustrative purpose and, on the basis of that system, some peculiar aspects of the malicious attacks are pointed ou

Digital Twins and Cultural Heritage Preservation: A Case Study of Best Practices and Reproducibility in Chiesa dei SS Apostoli e Biagio

The use of digital twin technologies to preserve cultural heritage has become increasingly common over the past two decades. Evolving from the use of virtual environments (VE) and digital reconstructions that required multiple phases of workflow and multiple software applications and various hardware to output a useable experience to the immediacy of 3D artificial intelligence (AI) generative content and the latest generation of photogrammetric scanning, non-specialists are now able to more easily create digital twins. At the same time, the destruction of cultural heritage has accelerated due to geopolitical instability, seen in examples such as the invasion of Ukraine by Russia (2022). Even with advances in user-friendly and commercially available technologies, digital art history and the digital humanities are in a race against time to train and equip enough individuals onsite to create digital twins before more irreplaceable cultural artifacts and sites are lost to natural disasters, accelerated by climate change, or through armed conflict. However, there remain no international standards for methodological reproducibility and the techniques used currently by many scholars include specialized training and knowledge. As such, this paper presents a case study that addresses reproducibility and explainability in the digital humanities through a detailed workflow of the creation of a digital twin of Chiesa dei SS Apostoli e Biagio in Florence, Italy. A model is presented that is scalable and leverages widely available, user-friendly 360 cameras and photogrammetry with LiDAR to capture cultural heritage sites with best practices on how to quickly and effectively train non-specialists to create site-specific digital twins of a variety of cultural heritage structures

A Paris Law Based Mesh Independent Numerical Methodology for the Simulation of Fatigue Driven Delamination in Composites

Delamination evolution under cyclic loading is one of the most important research topics for the application of composite materials to aerospace, naval, automotive and, in general, transportation fields. Large experimental campaigns are needed to assess the fatigue behavior of Carbon Fiber Reinforced Polymers (CFRPs), which may result extremely time and cost consuming. Nevertheless, composite materials design needs to take into account the evolution of fatigue driven damage. Subsequently, the development of efficient and robust computational finite element methodologies to evaluate progression of delamination in composite structural components subjected to cyclic loading conditions has become relevant. In this paper, a numerical finite element procedure able to simulate the fatigue driven delamination growth is introduced. A Paris-law based cycle jump strategy, combined with the Virtual Crack Closure Technique (VCCT) approach, has been implemented in the commercial Finite Element Code ANSYS MECHANICAL via the Ansys Parametric Design Language (APDL). The main advantages of the proposed numerical procedure, named FT-SMXB, are related to its independence on the time step and element size in the frame of incremental analyses. The procedure has been preliminary validated, in this research study, at coupon level, by comparing the numerical results to literature experimental data on a unidirectional graphite/epoxy Double Cantilever Beam (DCB) specimen. The significant agreement between the obtained numerical results and the literature experimental benchmark data confirms the accuracy and the potential of the proposed methodology

Determination of the prosumer's optimal bids

This paper considers a microgrid connected with a medium-voltage (MV) distribution network. It is assumed that the microgrid, which is managed by a prosumer, operates in a competitive environment and participates in the day-ahead market. Then, as the first step of the short-term management problem, the prosumer must determine the bids to be submitted to the market. The offer strategy is based on the application of an optimization model, which is solved for different hourly price profiles of energy exchanged with the main grid. The proposed procedure is applied to a microgrid and four different its configurations were analyzed. The configurations consider the presence of thermoelectric units that only produce electricity, a boiler or/and cogeneration power plants for the thermal loads, and an electric storage system. The numerical results confirmed the numerous theoretical considerations that have been made

NEW APPROACHES FOR VERY SHORT-TERM STEADY-STATE ANALYSIS OF AN ELECTRICAL DISTRIBUTION SYSTEM WITH WIND FARMS

Distribution networks are undergoing radical changes due to the high level of penetration of dispersed generation. Dispersed generation systems require particular attention due to their incorporation of uncertain energy sources, such as wind farms, and due to the impacts that such sources have on the planning and operation of distribution networks. In particular, the foreseeable, extensive use of wind turbine generator units in the future requires that distribution system engineers properly account for their impacts on the system. Many new technical considerations must be addressed, including protection coordination, steady-state analysis, and power quality issues. This paper deals with the very short-term, steady-state analysis of a distribution system with wind farms, for which the time horizon of interest ranges from one hour to a few hours ahead. Several wind-forecasting methods are presented in order to obtain reliable input data for the steady-state analysis. Both deterministic and probabilistic methods were considered and used in performing deterministic and probabilistic load-flow analyses. Numerical applications on a 17-bus, medium-voltage, electrical distribution system with various wind farms connected at different busbars are presented and discusse

Congenital rhabdomyosarcoma: a different clinical presentation in two cases

Background: Rhabdomyosarcoma (RMS), one of the most common soft tissue sarcomas of childhood, is very rare in the neonatal period (0.4-2% of cases). In order to gain a deeper understanding of this disease at such age, patient and tumor features, as well as treatment modality and outcome need to be reported. Case presentation: We describe two cases with congenital RMS treated at Bambino Gesù Children's Hospital between 2000 and 2016. They represent only 2.24% of all RMS patients diagnosed during that period in our Institution; this data is in agreement with the incidence reported in the literature. They reflect the two different clinical forms in which the disease may manifest itself. One patient, with the alveolar subtype (positive for specific PAX3-FOXO1 fusion transcript) and disseminated disease, had a fatal outcome with central nervous system (CNS) progression despite conventional and high dose chemotherapy. The other child, with the localized embryonal subtype, was treated successfully with conservative surgery and conventional chemotherapy, including prolonged maintenance therapy. He is disease free at 7 years of follow-up. Conclusions: RMS can also be diagnosed during the neonatal period. Given the young age, disease management is often challenging, and especially for the alveolar subtype, the outcome is dismal despite intensified multimodality therapy. In fact, it characteristically manifests with multiple subcutaneous nodules and progression most commonly occurs in the CNS (Rodriguez-Galindo et al., Cancer 92(6):1613-20, 2001). In this context, CNS prophylaxis could play a role in preventing leptomeningeal dissemination, and molecular studies can allow a deeper tumor characterization, treatment stratification and identification of new potential therapeutic targets

Delineating and Rationally Perturbing Signaling Mechanisms Involved in Metastasis

Metastasis is the dissemination of tumor cells from the primary locus of formation to other organs. During migration from the primary tumor, tumor cells need to traverse the vasculature, a process termed extravasation. Extravasation is a critical step in the metastatic cascade and nevertheless a poorly understood phenomenon. Endothelial cells form a barrier, which prevents cells and plasma constituents from moving into interstitial tissues. The disruption of the endothelial barrier leads to increased barrier permeability resulting in enhanced cancer cell extravasation. Protease-activated receptor-1 (PAR1) is a G protein-coupled receptor uniquely activated by proteases. PAR1 increases endothelial permeability when activated by the protease thrombin. Strikingly, PAR1 signaling can also mediate decreases in endothelial permeability when activated by activated protein C (APC), an anti-coagulant protease. In the first two chapters of this dissertation I examined the mechanism responsible for protease-selective signaling by PAR1. I specifically examined the effect of APC and thrombin on the activation of RhoA and Rac1 that differentially regulate endothelial permeability. In chapter 2 of this dissertation I also investigated whether compartmentalization of PAR1 in caveolae was critical for APC selective signaling and I demonstrated that caveolae are required for APC-selective signaling to Rac1 activation and endothelial barrier protection. Furthermore, in chapter 3 of this dissertation I asked whether APC protection from thrombin-induced increased permeability involved desensitization of PAR1. And I reported that APC induces PAR1 phosphorylation and desensitizes endothelial cells to thrombin. The metastatic process also requires degradation of extracellular matrices by proteases present in the tumor microenvironment, especially serine proteases. Inhibition of these proteases has remarkable therapeutic effects against tumor progression. Maspin is an atypical member of the family of serine proteases inhibitors. Maspin inhibits the serine protease urokinase activated plasminogen and suppresses tumor growth and metastasis. Interestingly, maspin is silenced by epigenetic mechanisms in cancer cells. In chapter 4 of my dissertation I used artificial transcription factors (ATFs) as a novel strategy to re-activate maspin in breast cancer cells. I showed that re-expression of maspin by ATFs leads to reduction of tumor growth and metastasis in an in vivo xenograft animal model