University of Calabria

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

In this paper we extend the "network theory of aging," and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as "inflamm-aging," is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.

Author(s): Collaboration, The ATLAS; Aad, G; Abat, E; Abdallah, J; Abdelalim, AA; Abdesselam, A; Abdinov, O; Abi, BA; Abolins, M; Abramowicz, H; Acerbi, E; Acharya, BS; Achenbach, R; Ackers, M; Adams, DL; Adamyan, F; Addy, TN; Aderholz, M; Adorisio, C; Adragna, P; Aharrouche, M; Ahlen, SP; Ahles, F; Ahmad, A; Ahmed, H; Aielli, G; Åkesson, PF; Åkesson, TPA; Akimov, AV; Alam, SM; Albert, J; Albrand, S; Aleksa, M; Aleksandrov, IN; Aleppo, M; Alessandria, F; Alexa, C; Alexander, G; Alexopoulos, T; Alimonti, G; Aliyev, M; Allport, PP; Allwood-Spiers, SE; Aloisio, A; Alonso, J; Alves, R; Alviggi, MG; Amako, K; Amaral, P; Amaral, SP; Ambrosini, G; Ambrosio, G; Amelung, C; Ammosov, VV; Amorim, A; Amram, N; Anastopoulos, C; Anderson, B; Anderson, KJ; Anderssen, EC; Andreazza, A; Andrei, V; Andricek, L; Andrieux, M-L; Anduaga, XS; Anghinolfi, F; Antonaki, A; Antonelli, M; Antonelli, S; Apsimon, R; Arabidze, G; Aracena, I; Arai, Y; Arce, ATH; Archambault, JP; Arguin, J-F; Arik, E; Arik, M; Arms, KE; Armstrong, SR; Arnaud, M; Arnault, C; Artamonov, A; Asai, S; Ask, S

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Cadmium (Cd) is a toxic non-essential transition metal that poses a health risk for both humans and animals. It is naturally occurring in the environment as a pollutant that is derived from agricultural and industrial sources. Exposure to cadmium primarily occurs through the ingestion of contaminated food and water and, to a significant extent, through inhalation and cigarette smoking. Cadmium accumulates in plants and animals with a long half-life of about 25–30 years. Epidemiological data suggest that occupational and environmental cadmium exposure may be related to various types of cancer, including breast, lung, prostate, nasopharynx, pancreas, and kidney cancers. It has been also demonstrated that environmental cadmium may be a risk factor for osteoporosis. The liver and kidneys are extremely sensitive to cadmium’s toxic effects. This may be due to the ability of these tissues to synthesize metallothioneins (MT), which are Cd-inducible proteins that protect the cell by tightly binding the toxic cadmium ions. The oxidative stress induced by this xenobiotic may be one of the mechanisms responsible for several liver and kidney diseases. Mitochondria damage is highly plausible given that these organelles play a crucial role in the formation of ROS (reactive oxygen species) and are known to be among the key intracellular targets for cadmium. When mitochondria become dysfunctional after exposure to Cd, they produce less energy (ATP) and more ROS. Recent studies show that cadmium induces various epigenetic changes in mammalian cells, both in vivo and in vitro, causing pathogenic risks and the development of various types of cancers. The epigenetics present themselves as chemical modifications of DNA and histones that alter the chromatin without changing the sequence of the DNA nucleotide. DNA methyltransferase, histone acetyltransferase, histone deacetylase and histone methyltransferase, and micro RNA are involved in the epigenetic changes. Recently, investigations of the capability of sunflower (Helianthus annuus L.), Indian mustard (Brassica juncea), and river red gum (Eucalyptus camaldulensis) to remove cadmium from polluted soil and water have been carried out. Moreover, nanoparticles of TiO2 and Al2O3 have been used to efficiently remove cadmium from wastewater and soil. Finally, microbial fermentation has been studied as a promising method for removing cadmium from food. This review provides an update on the effects of Cd exposure on human health, focusing on the cellular and molecular alterations involved.

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P F; F; C A; G; C J W P; T; V M; V A; G M; K Y; V; A L; I O; V N; S V; A G; A; A; A; A; E; W; M J; K K; P; H; R D; K F; A M; Smith, D S; R; M M; S; D; I; R; B A; A; F; Boyd, G R; P; G S; R; M; H; P; J; M; O; M; E; C; E; P; J; C; D; C; De C; De De J B; L; I; A C; L; D; G; S; J; L; P; M; I; M; G G R; P; J M; P; M; L; S; P; J P; D; G; A C; N; L; S; V M; E; D; J J; F; D; K; M; Y; L; T; D; K M; O; T; E; M J; F; K; Y; A L; B H; S; A; B; A; J P; D; G A N; C D; L; M; M; F G; M; V; M G; Yang, Z; A; P; A J; O; N D; de P A; D; P; J; M; C; E; M; J; E J; S M; L M; A; B M; F E W; Hill, J; D; A; D F; B T; C; M; Unel, M; Kirsch, G P; N; W; A; K; J; Lynn, J; A; R B; B; P; J C L; L; G H A; R; A R; Yang, S; G; A; P; F; M; F; S; F; D; M; D; B; Le O; I; F; M; L; A; P; S; F; P; M; M; C; R; M; A; M; G; M; D; A; D A; V; N; M; P T; B C; F F; A; F M; R; H H; F; M; V; E; T; A; V; P; V; A; E; C; F; I; Z; V; J; C; W; G; T; J; J; V; V; V; S; R; Zheng, W; M; J; J; J; M; I; M; P; V; O; A; V; O; M; M; M; M; M; S; M; I; 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K; M; I; M; V; T; W; U; M; I; R; S; S; S; C; D W; A; A; D; C; R K; K; B; A; D; H K; He, P; J; Y; R; D; A; R; Z; T; Lu, L; P; R R; R; A; Yang, J C; J; P; L; V; V; S; A; V P; S; L G; V P; S Y; F; V A; E; D M; I; A K; S M; B; S; F; L; A; B; R; G; J J; K; A; R L; M; J L; M; A; K J; P; B; Y; E; S; C; C; D; K; S; A; S O; Johansen, M; K E; K; J; D A; T; M; B; S B; J S H; L S; A F; K E; A T; M L; S; S C; Z; S C; D; Z; P K; S; Y; L; T; J; M; E G; H; G; N; G; M; O; Y; E; E; J; Y; Y; E; A; E; K; R; A; H; H; J; P; N; R; M; B; A; White, A; Yu, J; C; K; K; I A; A; A; C; D; I; U; C; S; M; M; N; M; Y; T; T; T; T; H; H; H; H; H; J; I; S; D C; A; P A; L S; B; K K; N K; P; Le C; Ma, L L; F K; J K; R; R S; Rosenbaum, G A; P; P; R J; W; K; Y; Y; T; Y; M; K; H; O; S; J; M; T; T; Y; Y; A; K; K; M; S; K; O; T; K; S; S; J; K; S; Y; A; H; Y; K; K; S H; T; A; Y; K; Y; F; W A; A; S; K; S; B S; D; M; De B; C; M P; H; L; L; C; N; R; E; T; M; M; C J; L; R; J; F; J; S; E; D; F; Segura, F; J; V; J V; M J; C S; C; F; A; 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In the last years membrane processes for gas separation are gaining a larger acceptance in industry and in the market are competing with consolidated operations such as pressure swing absorption and cryogenic distillation. The key for new applications of membranes in challenging and harsh environments (e.g., petrochemistry) is the development of new tough, high performance materials. The modular nature of membrane operations is intrinsically fit for process intensification, and this versatility might be a decisive factor to impose membrane processes in most gas separation fields, in a similar way as today membranes represent the main technology for water treatment. This review highlights the most promising areas of research in gas separation, by considering the materials for membranes, the industrial applications of membrane gas separations, and finally the opportunities for the integration of membrane gas separation units in hybrid systems for the intensification of processes.

Summary The kinematic understanding of the relationship between relative plate motion and the structure of orogenic belts depends upon a knowledge of relative plate motion across the plate boundary system, the relative motion of small blocks and flakes within the system, an evaluation of orogenic body forces, and an understanding of the thermomechanical evolution of the upper part of the orogenic lithosphere in determining strength and detachment levels. We have built a preliminary model for the Cenozoic kinematic evolution of the western Mediterranean oceanic basins and their peripheral orogens that integrates (1) the motion of Africa relative to Europe based upon a new study of Atlantic fracture zones using SEASAT data and the Lamont-Doherty magnetic anomaly database, (2) a new interpretation of the rotation of Corsica/Sardinia and the opening of the Balearic and Tyrrhenian oceanic basins, (3) sedimentary facies sequences in the Apennines, Calabria, and Sicily, and (4) Apennine/Calabrian structure and structural sequence.

Nickel is a transition element extensively distributed in the environment, air, water, and soil. It may derive from natural sources and anthropogenic activity. Although nickel is ubiquitous in the environment, its functional role as a trace element for animals and human beings has not been yet recognized. Environmental pollution from nickel may be due to industry, the use of liquid and solid fuels, as well as municipal and industrial waste. Nickel contact can cause a variety of side effects on human health, such as allergy, cardiovascular and kidney diseases, lung fibrosis, lung and nasal cancer. Although the molecular mechanisms of nickel-induced toxicity are not yet clear, mitochondrial dysfunctions and oxidative stress are thought to have a primary and crucial role in the toxicity of this metal. Recently, researchers, trying to characterize the capability of nickel to induce cancer, have found out that epigenetic alterations induced by nickel exposure can perturb the genome. The purpose of this review is to describe the chemical features of nickel in human beings and the mechanisms of its toxicity. Furthermore, the attention is focused on strategies to remove nickel from the environment, such as phytoremediation and phytomining.

A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is m_{H}=125.09±0.21 (stat)±0.11 (syst) GeV.

In this review we will focus on a topic of fundamental importance for both astrophysics and plasma physics, namely the occurrence of large-amplitude low-frequency fluctuations of the fields that describe the plasma state. This subject will be treated within the context of the expanding solar wind and the most meaningful advances in this research field will be reported emphasizing the results obtained in the past decade or so. As a matter of fact, Helios inner heliosphere and Ulysses' high latitude observations, recent multi-spacecrafts measurements in the solar wind (Cluster four satellites) and new numerical approaches to the problem, based on the dynamics of complex systems, brought new important insights which helped to better understand how turbulent fluctuations behave in the solar wind. In particular, numerical simulations within the realm of magnetohydrodynamic (MHD) turbulence theory unraveled what kind of physical mechanisms are at the basis of turbulence generation and energy transfer across the spectral domain of the fluctuations. In other words, the advances reached in these past years in the investigation of solar wind turbulence now offer a rather complete picture of the phenomenological aspect of the problem to be tentatively presented in a rather organic way.

Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3',5'-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator-activated receptor gamma coactivator 1alpha, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold was markedly reduced in brown adipose tissue of endothelial nitric oxide synthase null-mutant (eNOS-/-) mice, which had a reduced metabolic rate and accelerated weight gain as compared to wild-type mice. Thus, a nitric oxide-cGMP-dependent pathway controls mitochondrial biogenesis and body energy balance.

Disjunctive Logic Programming (DLP) is an advanced formalism for knowledge representation and reasoning, which is very expressive in a precise mathematical sense: it allows one to express every property of finite structures that is decidable in the complexity class Σ P 2 (NP NP ). Thus, under widely believed assumptions, DLP is strictly more expressive than normal ( disjunction-free ) logic programming, whose expressiveness is limited to properties decidable in NP. Importantly, apart from enlarging the class of applications which can be encoded in the language, disjunction often allows for representing problems of lower complexity in a simpler and more natural fashion.This article presents the DLV system, which is widely considered the state-of-the-art implementation of disjunctive logic programming, and addresses several aspects. As for problem solving, we provide a formal definition of its kernel language, function-free disjunctive logic programs (also known as disjunctive datalog ), extended by weak constraints, which are a powerful tool to express optimization problems. We then illustrate the usage of DLV as a tool for knowledge representation and reasoning, describing a new declarative programming methodology which allows one to encode complex problems (up to Δ P 3 -complete problems) in a declarative fashion. On the foundational side, we provide a detailed analysis of the computational complexity of the language of DLV, and by deriving new complexity results we chart a complete picture of the complexity of this language and important fragments thereof.Furthermore, we illustrate the general architecture of the DLV system, which has been influenced by these results. As for applications, we overview application front-ends which have been developed on top of DLV to solve specific knowledge representation tasks, and we briefly describe the main international projects investigating the potential of the system for industrial exploitation. Finally, we report about thorough experimentation and benchmarking, which has been carried out to assess the efficiency of the system. The experimental results confirm the solidity of DLV and highlight its potential for emerging application areas like knowledge management and information integration.

Phototaxis and photophobic responses of green algae are mediated by rhodopsins with microbial-type chromophores. We report a complementary DNA sequence in the green alga Chlamydomonas reinhardtii that encodes a microbial opsin-related protein, which we term Channelopsin-1. The hydrophobic core region of the protein shows homology to the light-activated proton pump bacteriorhodopsin. Expression of Channelopsin-1, or only the hydrophobic core, in Xenopus laevis oocytes in the presence of all-trans retinal produces a light-gated conductance that shows characteristics of a channel selectively permeable for protons. We suggest that Channelrhodopsins are involved in phototaxis of green algae.

This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.

Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a W or a Z boson or a pair of top quarks, and of the six decay modes H → ZZ, W W , γγ, ττ, bb, and μμ. All results are reported assuming a value of 125.09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton-proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fb$^{−1}$ at $\sqrt{s}$=7 TeV and 20 fb−1 at $\sqrt{s}$=8 TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1.09 ± 0.11. The combined measurements lead to observed significances for the vector boson fusion production process and for the H → ττ decay of 5.4 and 5.5 standard deviations, respectively. The data are consistent with the Standard Model predictions for all parameterisations considered.

We describe the synthesis of very thin sheets (between a few and ten atomic layers) of hexagonal boron nitride (h-BN), prepared either on a SiO2 substrate or freely suspended. Optical microscopy, atomic force microscopy, and transmission electron microscopy have been used to characterize the morphology of the samples and to distinguish between regions of different thicknesses. Comparison is made to previous studies on single- and few-layer graphene. This synthesis opens the door to experimentally accessing the two-dimensional phase of boron nitride.

Gold nanoparticles supported on P25 titania (Au/TiO(2)) exhibit photocatalytic activity for UV and visible light (532 nm laser or polychromatic light λ > 400 nm) water splitting. The efficiency and operating mechanism are different depending on whether excitation occurs on the titania semiconductor (gold acting as electron buffer and site for gas generation) or on the surface plasmon band of gold (photoinjection of electrons from gold onto the titania conduction band and less oxidizing electron hole potential of about -1.14 V). For the novel visible light photoactivity of Au/TiO(2), it has been determined that gold loading, particle size and calcination temperature play a role in the photocatalytic activity, the most active material (Φ(H2) = 7.5% and Φ(O2) = 5.0% at 560 nm) being the catalyst containing 0.2 wt % gold with 1.87 nm average particle size and calcined at 200 °C.

Magnetic storage based on racetrack memory is very promising for the design of ultra-dense, low-cost and low-power storage technology. Information can be coded in a magnetic region between two domain walls or, as predicted recently, in topological magnetic objects known as skyrmions. Here, we show the technological advantages and limitations of using Bloch and Néel skyrmions manipulated by spin current generated within the ferromagnet or via the spin-Hall effect arising from a non-magnetic heavy metal underlayer. We found that the Néel skyrmion moved by the spin-Hall effect is a very promising strategy for technological implementation of the next generation of skyrmion racetrack memories (zero field, high thermal stability, and ultra-dense storage). We employed micromagnetics reinforced with an analytical formulation of skyrmion dynamics that we developed from the Thiele equation. We identified that the excitation, at high currents, of a breathing mode of the skyrmion limits the maximal velocity of the memory.

Essential oils are complex mixtures of hydrocarbons and their oxygenated derivatives arising from two different isoprenoid pathways. Essential oils are produced by glandular trichomes and other secretory structures, specialized secretory tissues mainly diffused onto the surface of plant organs, particularly flowers and leaves, thus exerting a pivotal ecological role in plant. In addition, essential oils have been used, since ancient times, in many different traditional healing systems all over the world, because of their biological activities. Many preclinical studies have documented antimicrobial, antioxidant, anti-inflammatory and anticancer activities of essential oils in a number of cell and animal models, also elucidating their mechanism of action and pharmacological targets, though the paucity of in human studies limits the potential of essential oils as effective and safe phytotherapeutic agents. More well-designed clinical trials are needed in order to ascertain the real efficacy and safety of these plant products.