Expressiveness and complexity of graph logic

We investigate the complexity and expressive power of the spatial logic for querying graphs introduced by Cardelli, Gardner and Ghelli (ICALP 2002).We show that the model-checking complexity of versions of this logic with and without recursion is PSPACE-complete. In terms of expressive power, the version without recursion is a fragment of the monadic second-order logic of graphs and we show that it can express complete problems at every level of the polynomial hierarchy. We also show that it can define all regular languages, when interpretation is restricted to strings. The expressive power of the logic with recursion is much greater as it can express properties that are PSPACE-complete and therefore unlikely to be definable in second-order logic

Organization of the respiratory supercomplexes in cells with defective complex III: Structural features and metabolic consequences

The mitochondrial respiratory chain encompasses four oligomeric enzymatic complexes (complex I, II, III and IV) which, together with the redox carrier ubiquinone and cytochrome c, catalyze electron transport coupled to proton extrusion from the inner membrane. The protonmotive force is utilized by complex V for ATP synthesis in the process of oxidative phosphorylation. Respiratory complexes are known to coexist in the membrane as single functional entities and as supramolecular aggregates or supercomplexes (SCs). Understanding the assembly features of SCs has relevant biomedical implications because defects in a single protein can derange the overall SC organization and compromise the energetic function, causing severe mitochondrial disorders. Here we describe in detail the main types of SCs, all characterized by the presence of complex III. We show that the genetic alterations that hinder the assembly of Complex III, not just the activity, cause a rearrangement of the architecture of the SC that can help to preserve a minimal energetic function. Finally, the major metabolic disturbances associated with severe SCs perturbation due to defective complex III are discussed along with interventions that may circumvent these deficiencies

Regular Expression Subtyping for XML Query and Update Languages

XML database query languages such as XQuery employ regular expression types with structural subtyping. Subtyping systems typically have two presentations, which should be equivalent: a declarative version in which the subsumption rule may be used anywhere, and an algorithmic version in which the use of subsumption is limited in order to make typechecking syntax-directed and decidable. However, the XQuery standard type system circumvents this issue by using imprecise typing rules for iteration constructs and defining only algorithmic typechecking, and another extant proposal provides more precise types for iteration constructs but ignores subtyping. In this paper, we consider a core XQuery-like language with a subsumption rule and prove the completeness of algorithmic typechecking; this is straightforward for XQuery proper but requires some care in the presence of more precise iteration typing disciplines. We extend this result to an XML update language we have introduced in earlier work.Comment: ESOP 2008. Companion technical report with proof

Melanopsin-expressing retinal ganglion cells are resistant to cell injury, but not always

Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs deputed to non-image forming functions of the eye such as synchronization of circadian rhythms to light-dark cycle. These cells are characterized by unique electrophysiological, anatomical and biochemical properties and are usually more resistant than conventional RGCs to different insults, such as axotomy and different paradigms of stress. We also demonstrated that these cells are relatively spared compared to conventional RGCs in mitochondrial optic neuropathies (Leber's hereditary optic neuropathy and Dominant Optic Atrophy). However, these cells are affected in other neurodegenerative conditions, such as glaucoma and Alzheimer's disease. We here review the current evidences that may underlie this dichotomy. We also present our unpublished data on cell experiments demonstrating that melanopsin itself does not explain the robustness of these cells and some preliminary data on immunohistochemical assessment of mitochondria in mRGCs

The cell cycle checkpoint inhibitors in the treatment of leukemias

open3noThe study was funded by the University of Bologna and by the Italian Association for Cancer Research (AIRC).The inhibition of the DNA damage response (DDR) pathway in the treatment of cancers has recently reached an exciting stage with several cell cycle checkpoint inhibitors that are now being tested in several clinical trials in cancer patients. Although the great amount of pre-clinical and clinical data are from the solid tumor experience, only few studies have been done on leukemias using specific cell cycle checkpoint inhibitors. This review aims to summarize the most recent data found on the biological mechanisms of the response to DNA damages highlighting the role of the different elements of the DDR pathway in normal and cancer cells and focusing on the main genetic alteration or aberrant gene expression that has been found on acute and chronic leukemias. This review, for the first time, outlines the most important pre-clinical and clinical data available on the efficacy of cell cycle checkpoint inhibitors in single agent and in combination with different agents normally used for the treatment of acute and chronic leukemias.openGhelli Luserna di Rora', A; Iacobucci, I; Martinelli, GGhelli Luserna di Rora', A; Iacobucci, I; Martinelli,

El Centro Europeo de Predicción a Medio Plazo

El Centro Europeo de Predicción a Medio Plazo es puntero a nivel mundial en la predicción numérica, y su estrategia de futuro apuesta decididamente por la predicción probabilista. Nos proponemos contar en qué consiste este organismo, quiénes lo integran, cómo se trabaja allí (y dónde es allí) y qué se hace. Qué son el IFS, el HRES, el ENS, y por qué son tan reconocidos en el mundo de la predicción meteorológica. Cómo funciona el sistema de predicción por conjuntos del Centro Europeo y por qué la estrategia del centro se vuelca en un ambicioso desarrollo de dicho sistema. Cuál es la participación española en la institución. La «brecha de género» que aqueja al mundo científico en general y meteorológico en particular, ¿se refleja también en un organismo tan prestigioso como éste? Y, como el propio presidente del organismo, lo resumimos todo en dos palabras: «Más colaboración»

Validation of Modern JSON Schema: Formalization and Complexity

JSON Schema is the de-facto standard schema language for JSON data. The language went through many minor revisions, but the most recent versions of the language, starting from Draft 2019-09, added two novel features, dynamic references and annotation-dependent validation, that change the evaluation model. Modern JSON Schema is the name used to indicate all versions from Draft 2019-09, which are characterized by these new features, while Classical JSON Schema is used to indicate the previous versions. These new "modern"features make the schema language quite difficult to understand and have generated many discussions about the correct interpretation of their official specifications; for this reason, we undertook the task of their formalization. During this process, we also analyzed the complexity of data validation in Modern JSON Schema, with the idea of confirming the polynomial complexity of Classical JSON Schema validation, and we were surprised to discover a completely different truth: data validation, which is expected to be an extremely efficient process, acquires, with Modern JSON Schema features, a PSPACE complexity. In this paper, we give the first formal description of Modern JSON Schema, which we have discussed with the community of JSON Schema tool developers, and which we consider a central contribution of this work. We then prove that its data validation problem is PSPACE-complete. We prove that the origin of the problem lies in the Draft 2020-12 version of dynamic references, and not in annotation-dependent validation. We study the schema and data complexities, showing that the problem is PSPACE-complete with respect to the schema size even with a fixed instance but is in P when the schema is fixed and only the instance size is allowed to vary. Finally, we run experiments that show that there are families of schemas where the difference in asymptotic complexity between dynamic and static references is extremely visible, even with small schemas

The formation of SCEs as an effect of occupational exposure to formaldehyde

Formaldehyde (FA) is a ubiquitous toxic chemical employed worldwide due to its disinfectant and preservative properties. Despite being classified as a human carcinogen, FA is still employed as formalin in pathology wards as standard fixative. We evaluated its relationship with the formation of sister-chromatid exchanges (SCEs) in cultured peripheral blood lymphocytes on 57 pathologists and 48 controls and the risk/protective role played by several genetic polymorphisms. All subjects were assessed for SCEs and genotyped for the most common cancer-associated gene polymorphisms: CYP1A1 exon 7 (A > G), CYP1A1*2A (T > C), CYP2C19*2 (G > A), GSTT1 (presence/absence), GSTM1 (presence/absence), GSTP1 (A > G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα − 308 G > A), IL10 − 1082 (G > A), and IL6 − 174 (G > C). Air-FA concentration was assessed through passive personal samplers. Pathologists, exposed to 55.2 μg/m(3) of air-FA, showed a significantly higher SCEs frequency than controls, exposed, respectively, to 18.4 μg/m(3). Air-FA was directly correlated with SCEs frequency and inversely with the replication index (RI). Regression models showed FA exposure as a significant predictor in developing SCEs, while did not highlight any role of the selected polymorphisms. Our study confirms the role of low air-FA levels as genotoxicity inductor, highlighting the importance to define exposure limits that could be safer for exposed workers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00204-022-03238-w

CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies

Cell division cycle 20 homologue (CDC20) is a well-known regulator of cell cycle, as it controls the correct segregation of chromosomes during mitosis. Many studies have focused on the biological role of CDC20 in cancer development, as alterations of its functionality have been linked to genomic instability and evidence demonstrated that high CDC20 expression levels are associated with poor overall survival in solid cancers. More recently, novel CDC20 functions have been demonstrated or suggested, including the regulation of apoptosis and stemness properties and a correlation with immune cell infiltration. Here, we here summarize and discuss the role of CDC20 inside and outside mitosis, starting from its network of interacting proteins. In the last years, CDC20 has also attracted more interest in the blood cancer field, being overexpressed and showing an association with prognosis both in myeloid and lymphoid malignancies. Preclinical findings showed that selective CDC20 and APC/CCDC20/APC/CCDH1 inhibitors, namely Apcin and proTAME, are effective against lymphoma and multiple myeloma cells, resulting in mitotic arrest and apoptosis and synergizing with clinically-relevant drugs. The evidence and hypothesis presented in this review provide the input for further biological and chemical studies aiming to dissect novel potential CDC20 roles and targeting strategies in hematological malignancies