Gene expression profiling of Mycobacterium avium subsp. paratuberculosis in simulated multi-stress conditions and within THP-1 cells reveals a new kind of interactive intramacrophage behaviour

Recent studies have identified in Mycobacterium avium subsp. paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans. Therefore, considering the possible risk for public health, it is necessary a thorough understanding of MAP's gene expression during infection of human host as well as the identification of its immunogenic and/or virulence factors for the development of appropriate diagnostic and therapeutic tools.In order to characterize MAP's transcriptome during macrophage infection, we analyzed for the first time the whole gene expression of a human derived strain of MAP in simulated intraphagosomal conditions and after intracellular infection of the human macrophage cell line THP-1 by using the DNA-microarray technology. Results showed that MAP shifts its transcriptome to an adaptive metabolism for an anoxic environment and nutrient starvation. It up-regulates several response factors to oxidative stress or intracellular conditions and allows, in terms of transcription, a passive surface peptidoglycan spoliation within the macrophage along with an intensification of the anabolic activity for lipidic membrane structures.These results indicate a possible interactive system between MAP and its host cell based on the internal mimicry unlike other intracellular pathogens, bringing new hypothesis in the virulence and pathogenicity of MAP and its importance in human health

The close relationship between the Golgi trafficking machinery and protein glycosylation

La glicosilazione è la più comune modifica post-traduzionale delle proteine; media la loro corretta piegatura e stabilità, nonché il loro trasporto attraverso il trasporto secretorio. I cambiamenti nei glicani legati all'N e all'O sono stati associati a molteplici condizioni patologiche tra cui disturbi congeniti della glicosilazione, malattie infiammatorie e cancro. La glicosilazione della glicoproteina al Golgi coinvolge l'azione coordinata di centinaia di glicosiltransferasi e glicosidasi, che vengono mantenute nella posizione corretta attraverso il traffico di vescicole retrograde tra le cisterne di Golgi. In questa recensione, descriviamo il macchinario molecolare coinvolto nel traffico di vescicole e nel tethering presso l'apparato di Golgi e gli effetti delle mutazioni nel contesto della biosintesi dei glicani e delle malattie umane.Glycosylation is the most common post-translational modification of proteins; it mediates their correct folding and stability, as well as their transport through the secretory transport. Changes in N- and O-linked glycans have been associated with multiple pathological conditions including congenital disorders of glycosylation, inflammatory diseases and cancer. Glycoprotein glycosylation at the Golgi involves the coordinated action of hundreds of glycosyltransferases and glycosidases, which are maintained at the correct location through retrograde vesicle trafficking between Golgi cisternae. In this review, we describe the molecular machinery involved in vesicle trafficking and tethering at the Golgi apparatus and the effects of mutations in the context of glycan biosynthesis and human diseases

resolution of rate related left bundle branch block after nitrate therapy

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A bottom-up appraisal of the technically installable capacity of biogas-based solid oxide fuel cells for self power generation in wastewater treatment plants

This paper proposes a bottom-up method to estimate the technical capacity of solid oxide fuel cells to be installed in wastewater treatment plants and valorise the biogas obtained from the sludge through an efficient conversion into electricity and heat. The methodology uses stochastic optimisation on 200 biogas profile scenarios generated from industrial data and envisages a Pareto approach for an a posteriori assessment of the optimal number of generation unit for the most representative plant configuration sizes. The method ensures that the dominant role of biogas fluctuation is included in the market potential and guarantees that the utilization factor of the modules remains higher than 70% to justify the investment costs. Results show that the market potential for solid oxide fuel cells across Europe would lead up to 1,300 MW of installed electric capacity in the niche market of wastewater treatment and could initiate a capital and fixed costs reduction which could make the technology comparable with alternative combined heat and power solutions

Oncogenic roles of GOLPH3 in the physiopathology of cancer

Golgi phosphoprotein 3 (GOLPH3), un effettore del fosfatidilinositolo 4-fosfato [PI (4) P] al Golgi, è necessaria per il mantenimento della struttura del nastro del Golgi, il traffico di vescicole e la glicosilazione del Golgi. GOLPH3 è stato convalidato come oncoproteina combinando la genomica integrativa con l'analisi clinopatologiche e funzionali. È spesso amplificato in diversi tipi di tumori solidi tra cui melanoma, cancro ai polmoni, cancro al seno, glioma e cancro del colon-retto. La sovraespressione di GOLPH3 è correlata a una prognosi infausta in più tipi di tumore, compreso il 52% dei tumori al seno e dal 41% al 53% del glioblastoma. I ruoli di GOLPH3 nella tumorigenesi possono essere correlati a diverse attività cellulari, tra cui: (i) regolazione del traffico dal Golgi alla membrana plasmatica e contributo a fenotipi secretori maligni; (ii) controllare l'internalizzazione e il riciclaggio di molecole di segnalazione chiave o aumentare la glicosilazione delle glicoproteine ​​rilevanti per il cancro; e (iii) influenzare la risposta al danno al DNA e il mantenimento della stabilità genomica. Qui riassumiamo le attuali conoscenze sui percorsi oncogeni che coinvolgono GOLPH3 nel cancro umano, l'influenza di GOLPH3 sul metabolismo del tumore e sullo stroma circostante e il suo possibile ruolo nella formazione di metastasi tumorali.Golgi phosphoprotein 3 (GOLPH3), a Phosphatidylinositol 4-Phosphate [PI(4)P] effector at the Golgi, is required for Golgi ribbon structure maintenance, vesicle trafficking and Golgi glycosylation. GOLPH3 has been validated as an oncoprotein through combining integrative genomics with clinopathological and functional analyses. It is frequently amplified in several solid tumor types including melanoma, lung cancer, breast cancer, glioma, and colorectal cancer. Overexpression of GOLPH3 correlates with poor prognosis in multiple tumor types including 52% of breast cancers and 41% to 53% of glioblastoma. Roles of GOLPH3 in tumorigenesis may correlate with several cellular activities including: (i) regulating Golgi-to-plasma membrane trafficking and contributing to malignant secretory phenotypes; (ii) controlling the internalization and recycling of key signaling molecules or increasing the glycosylation of cancer relevant glycoproteins; and (iii) influencing the DNA damage response and maintenance of genomic stability. Here we summarize current knowledge on the oncogenic pathways involving GOLPH3 in human cancer, GOLPH3 influence on tumor metabolism and surrounding stroma, and its possible role in tumor metastasis formation

Employment of portable gamma-ray spectrometer in survey and mapping of intrusive complexes: a case study from the Buddusò pluton (Sardinia)

http://www.fe.infn.it/u/mantovani/CV/Proceedings/Puccini_10a.pd

Natural radioactivity in Sardinian granite dimension stones

http://www.fe.infn.it/u/mantovani/CV/Proceedings/Puccini_10b.pd

TOWARDS MODELS OF REALISTIC COMPUTING MACHINES IN COMPUTER SCIENCE

The paper presents an approach to system modelling in design of both hardware and software systems. It is based on the definition of models of machines that can be directly implemented. The paper shows how to render less abstract and more realistic the abstract machines defined by theoreticians, so that they can capture implementation and technological-oriented aspects, such as testability, and allow an easy transition to final implementations. A realistic abstract machine for lambda-calculus is then presented and the design of system for lambda-expressions evaluation is illustrated. The architecture chosen for the system is based on a collection of finite state automata, evolving concurrently and communicating via a broadcast system. Some conclusive remarks about the use of realistic models arc finally drawn

Alcohol Intake and Arterial Hypertension: Retelling of a Multifaceted Story

Alcoholic beverages are common components of diets worldwide and understanding their effects on humans’ health is crucial. Because hypertension is the leading risk factor for cardiovascular diseases and all-cause mortality, the relationship of alcohol consumption with blood pressure (BP) has been the subject of extensive investigation. For the purpose of this review, we searched the terms “alcohol”, “ethanol”, and “arterial hypertension” on Pubmed MeSH and selected the most relevant studies. Short-term studies showed a biphasic BP response after ingestion of high doses of alcohol, and sustained alcohol consumption above 30 g/day, significantly, and dose-dependently, increased the risk for hypertension. These untoward effects of alcoholic beverages on BP can be mediated by a multiplicity of neurohormonal mechanisms. In addition to the effects on BP, excess alcohol intake might contribute to cardiac and renal hypertensive organ damage, although some studies suggest possible benefits of moderate alcohol consumption on additional cardiovascular risk factors, such as diabetes and lipoprotein(a). Some intervention studies and cumulative analyses support the evidence of a benefit of the reduction/withdrawal of alcohol consumption on BP and cardiovascular outcomes. This is why guidelines of scientific societies recommend avoidance or limitation of alcohol intake below one unit/day for women and two units/day for men. This narrative article overviews all these topics, providing an update of the current knowledge on the relationship between alcohol and BP